Journal of Pathology and Translational Medicine

Original Articles

Serous Adenocarcinoma of Fallopian Tubes: Histological and Immunohistochemical Aspects: Natalia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Artem Piddubnyi, Ludmila Karpenko, Olha Kravtsova, Dmytrii Hyriavenko, Olena Diachenko, Vladyslav Sikora, Anatolii Romaniuk; J Pathol Transl Med. 2019;53(4):236-243. Published online April 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.03.21

8,497 View
132 Download
4 Web of Science
5 Crossref

Background
Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype.
Methods
The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics.
Results
ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy.
Conclusions
Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.

Citations

Citations to this article as recorded by

Rare non-serous fallopian tube cancers: institutional experience and literature review
Dmitrii Sumtsov, Georgyi Sumtsov, Nataliia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Nataliia Kalashnik, Svitlana Smiian, Igor Gladchuk
Wiener Medizinische Wochenschrift.2024; 174(9-10): 199. CrossRef
UŞAQLIQ BORULARININ BİRİNCİLİ XƏRÇƏNGİ: DİAQNOSTİKASI VƏ MÜALİCƏSİNİN NƏTİCƏLƏRİ
D.G. Sumtsov, G.O. Sumtsov, N.I. Hyriavenko, S.A. Smiian, N.V. Kalashnyk, K.O. Sikora, N.M. Rozhkovska, I.Z. Gladchuk
Azerbaijan Medical Journal.2023; (4): 75. CrossRef
FEATURES OF ENDOMETRIUM STRUCTURE IN ALCOHOL-ABUSING HIV-INFECTED INDIVIDUALS
M. Lytvynenko
Inter Collegas.2021; 8(1): 52. CrossRef
Concurrent Clostridial Enteritis and Oviductal Adenocarcinoma with Carcinomatosis in an Adult Alpaca (Vicugna pacos)
Mandy Womble, Megan E. Schreeg, Allison Hoch, Enoch B. de Souza Meira, Derek Foster, Christopher Premanandan, Tatiane T. Negrão Watanabe
Journal of Comparative Pathology.2021; 189: 52. CrossRef
Problems of primary fallopian tube cancer diagnostics during and after surgery
D.G. Sumtsov, I.Z. Gladchuk, G.O. Sumtsov, N.I. Hyriavenko, M.S. Lyndin, V.V. Sikora, V.M. Zaporozhan
REPRODUCTIVE ENDOCRINOLOGY.2021; (59): 66. CrossRef

Expression of Human Papillomavirus-Related Proteins and Its Clinical Implication in Tonsillar Squamous Cell Carcinoma: Joon Seon Song, Min-Sik Kim, Joon Wook Park, Youn Soo Lee, Chang Suk Kang; Korean J Pathol. 2012;46(2):177-186. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.177

11,001 View
42 Download
9 Crossref

Abstract PDF

Background

Human papillomavirus (HPV) is known to cause of oropharyngeal squamous cell carcinoma (SqCC). HPV positive SqCCs overexpress p16 and are associated with better survival. Several markers of cell cycles and apoptosis have been reported as a prognostic value. We examined the prognostic value of HPV status, p16, cyclin D1, and Bcl-2 in patients with tonsillar SqCC.

Methods

Tissue microarrays were constructed in 56 cases of tonsillar SqCC for which we performed an immunohistochemistry and an in situ hybridization (ISH) of the HPV.

Results

Of the 56 cases, 31 (55.3%) were positive for p16 and 20 (35.7%) were positive for HPV ISH. The expressions of p16, cyclin D1, and Bcl-2 were not correlated with the clinicopathologic variables including smoking status, differentiation and pT- and pN-stages. The HPV ISH positive group showed a better overall survival than the HPV negative group (p=0.04), and the p16 positive group showed a better disease free survival (DFS) than the negative group (p=0.016). Cox regression analysis showed that only p16 positivity was an independent prognostic factor for DFS (p=0.03; hazard ratio, 10.1).

Conclusions

Our results indicate that both p16 expression and HPV status are useful indicators for risk stratification in patients with tonsillar SqCC.

Citations

Citations to this article as recorded by

Positive Rate of Human Papillomavirus and Its Trend in Head and Neck Cancer in South Korea
Hyun Woong Jun, Yong Bae Ji, Chang Myeon Song, Jae Kyung Myung, Hae Jin Park, Kyung Tae
Frontiers in Surgery.2022;[Epub] CrossRef
Negative Prognostic Implication of TERT Promoter Mutations in Human Papillomavirus–Negative Tonsillar Squamous Cell Carcinoma Under the New 8th AJCC Staging System
Hyunchul Kim, Mi Jung Kwon, Bumjung Park, Hyo Geun Choi, Eun Sook Nam, Seong Jin Cho, Kyueng-Whan Min, Eun Soo Kim, Hee Sung Hwang, Mineui Hong, Taeryool Koo, Hyo Jung Kim
Indian Journal of Surgical Oncology.2021; 12(S1): 134. CrossRef
In situ hybridization for high risk HPV E6/E7 mRNA in oropharyngeal squamous cell carcinoma
Krish Suresh, Parth V. Shah, Sydney Coates, Borislav A. Alexiev, Sandeep Samant
American Journal of Otolaryngology.2021; 42(1): 102782. CrossRef
Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas
Yuil Kim, Young-Hoon Joo, Min-Sik Kim, Youn Soo Lee
Journal of Pathology and Translational Medicine.2020; 54(5): 411. CrossRef
Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists
James S. Lewis, Beth Beadle, Justin A. Bishop, Rebecca D. Chernock, Carol Colasacco, Christina Lacchetti, Joel Todd Moncur, James W. Rocco, Mary R. Schwartz, Raja R. Seethala, Nicole E. Thomas, William H. Westra, William C. Faquin
Archives of Pathology & Laboratory Medicine.2018; 142(5): 559. CrossRef
Detection of HPV infection in head and neck cancers: Promise and pitfalls in the last ten years: A meta-analysis
Carolin G�tz, Clara Bischof, Klaus-Dietrich Wolff, Andreas Kolk
Molecular and Clinical Oncology.2018;[Epub] CrossRef
Frequent hepatocyte growth factor overexpression and low frequency of c-Met gene amplification in human papillomavirus–negative tonsillar squamous cell carcinoma and their prognostic significances
Mi Jung Kwon, Dong Hoon Kim, Hye-Rim Park, Hyung Sik Shin, Ji Hyun Kwon, Dong Jin Lee, Jin Hwan Kim, Seong Jin Cho, Eun Sook Nam
Human Pathology.2014; 45(7): 1327. CrossRef
Human papillomavirus‐stratified analysis of the prognostic role of miR‐21 in oral cavity and oropharyngeal squamous cell carcinoma
Yoon Ho Ko, Hye Sung Won, Der Sheng Sun, Ho Jung An, Eun Kyoung Jeon, Min Sik Kim, Han Hong Lee, Jin Hyoung Kang, Chan Kwon Jung
Pathology International.2014; 64(10): 499. CrossRef
Human Papillomavirus Prevalence and Cell Cycle Related Protein Expression in Tonsillar Squamous Cell Carcinomas of Korean Patients with Clinicopathologic Analysis
Miji Lee, Sung Bae Kim, Sang-wook Lee, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Kyung-Ja Cho
Korean Journal of Pathology.2013; 47(2): 148. CrossRef

Case Reports

In Situ Follicular Lymphoma Developed after Hodgkin Lymphoma.: Ho Sung Park, Sang Jae Noh, Jae Yong Kwak, Eun Kee Song, Myung Hee Sohn, Ho Lee, Woo Sung Moon, Kyu Yun Jang; Korean J Pathol. 2011;45:S53-S57.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S53

3,872 View
23 Download

Abstract PDF: In situ follicular lymphoma is a newly defined entity among the lymphoid neoplasms and is defined as architecturally normal-appearing lymph nodes and other lymphoid tissues that have one or more follicles that demonstrate bcl-2 overexpressing centrocytes and centroblasts, with or without a monomorphic cytologic appearance suggestive of follicular lymphoma. Here we present a case of in situ follicular lymphoma diagnosed during the follow-up after a complete response to the treatment of lymphocyte-rich classical Hodgkin's lymphoma. In our case, because only a few germinal centers contained bcl-2 overexpressing cells, we missed the diagnosis of in situ follicular lymphoma in the initial histological examination. We could establish the diagnosis only after performing bcl-2 immunostaining in the sequential biopsy. Therefore, we recommend that careful histological examination along with bcl-2 immunostaining is needed in patients with suspicious clinical findings.

Solitary Fibrous Tumor of the Conjunctiva with Heretofore Undescribed Pathologic Findings.: Na Rae Kim, Jae Y Ro, Kyung Hwan Shin, Hae Jung Paik, Jung Suk An, Seung Yeon Ha; Korean J Pathol. 2011;45(3):315-318.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.315

4,552 View
27 Download
1 Crossref

Abstract PDF

A 37-year-old female presented with a conjunctival mass discovered 3 years prior. An excisional biopsy revealed a patternless proliferation of round and spindle-shaped cells with an eosinophilic fibrillary cytoplasm and vesicular nuclei with occasional inclusions. Psammoma bodies were arranged around the dilated irregularly-shaped vessels. Differential diagnoses included conjunctival solitary fibrous tumor (SFT), nevus, glomangioma, ectopic meningioma, and mesectodermal leiomyoma. The tumor cells were immunoreactive for CD34, CD99, bcl-2 and vimentin, and were negative for smooth muscle actin, desmin, glial fibrillary acidic protein, S-100 protein, epithelial membrane antigen, and human melanoma black-45. Ultrastructurally, the tumor cells had rough endoplasmic reticulum, free ribosomes, and scattered mitochondria without basal lamina or cellular junctions, which are features of fibroblasts. A diagnosis of SFT was rendered based on the light microscopic, immunohistochemical, and electron microscopic findings. We report here on the second case of a SFT arising in the conjunctiva, which clinically and histologically mimics conjunctival nevus, glomangioma, ectopic meningioma, and a hybrid neurogenic-myogenic tumor such as mesectodermal leiomyoma.

Citations

Citations to this article as recorded by

Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis
Nayoung Han, Hannah Kim, Soo Kee Min, Sun-Ha Paek, Chul-Kee Park, Seung-Hong Choi, U-Ri Chae, Sung-Hye Park
Journal of Pathology and Translational Medicine.2016; 50(2): 113. CrossRef

Original Articles

Alteration of Apoptosis-Related Proteins (Apaf-1, Caspase-9, Bcl-2, p53, and Survivin) According to Malignant Progression in Cutaneous Melanocytic Lesions.: Yeo Ju Kang, Ji Han Jung, Kwnag Il Yim, Kyo Young Lee, Youn Soo Lee, Seok Jin Kang, Chang Suk Kang, Si Yong Kim; Korean J Pathol. 2011;45(3):247-253.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.247

3,978 View
34 Download

Abstract PDF: BACKGROUND
Apoptosis protease activating factor-1 (Apaf-1), caspase-9, Bcl-2, p53, and survivin are important factors in the pathway of apoptosis, but their clinicopathologic significance remains unclear in human cutaneous melanoma. We investigated the expression of these proteins and their clinical value in human cutaneous melanocytic lesions.
METHODS
We performed an immunohistochemical analysis to examine the expression and distribution of Apaf-1, caspase-9, Bcl-2, p53, and survivin in 36 cases of malignant melanoma (22 cases of primary melanoma and 14 cases of metastatic melanoma) and 41 cases of melanocytic nevus.
RESULTS
The expression of p53 was significantly higher in malignant melanoma than in melanocytic nevus (p<0.01), however the expressions of Apaf-1 and caspase-9 were significantly lower in malignant melanoma compared with melanocytic nevus (p<0.01 and p=0.027, respectively). Also, there was a significant difference for Bcl-2 staining between primary melanomas and metastatic lesions (p=0.004). Nuclear staining for survivin were absent in nevus, but were positive in 14 of 36 melanomas (p<0.01).
CONCLUSIONS
The altered expression of Apaf-1, caspase-9, p53, and survivin are considered to be related to malignant progression in human cutaneous melanocytic lesions. Loss of Bcl-2 can be considered as a prognostic marker of malignant melanomas.

Distinction of Pulmonary Large Cell Neuroendocrine Carcinoma from Small Cell Lung Carcinoma Using a Panel of Bcl-2, p63, and 34betaE12.: Jun Zhe Li, Chan Choi, Yoo Duk Choi, Kook Joo Na; Korean J Pathol. 2011;45(2):170-174.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.170

3,881 View
33 Download
1 Crossref

Abstract PDF

BACKGROUND
Making the distinction between large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is difficult in some samples of biopsy tissues, but we have to separate LCNEC from SCLC because the two types of cancer may need different therapy and they have different prognostic implications. Thus far, there are no specific immunohistochemical markers that allow distinguishing these two kinds of tumors.
METHODS
We performed an immunohistochemical analysis to study the expressions of p63, Bcl-2, and 34betaE12 and to investigate whether these 3 molecules have correlations in LCNEC and SCLC. We also evaluated the expression of the neuroendocrine markers chromogranin, synaptophysin and CD56.
RESULTS
A statistical analysis was performed for p63, Bcl-2, and 34betaE12 in separate and combined panels. According to the combinations of p63, Bcl-2, and 34betaE12, there were frequent expressions of p63-/Bcl-2+ or Bcl-2+/34betaE12- in the SCLC, and there was a superior proportion of them in the SCLC rather than that in the LCNEC. The p63-/Bcl-2+ and Bcl-2+/34betaE12- antibody combinations showed higher specificities compared to any single antibody for diagnosing SCLC.
CONCLUSIONS
Bcl-2 and selective p63 or 34betaE12 made up a most useful panel of markers for making the differential diagnosis of LCNEC and SCLC.

Citations

Citations to this article as recorded by

Evaluation of Serum LDH, p53 and BCL2 in Lung Cancer Patients
Pawar Komal, Rajvik Kruti, Vora Hemangini
Gujarat Cancer Society Research Journal.2020; 22(2): 22. CrossRef

p16INK4a, PTEN, E-cadherin, Bcl-2 and Ki-67 Expression in Prostate Cancer: Its Relationship with the Metastatic Potential and Known Prognostic Factors.: Seok Ju Park, Woo Jung Sung, Mi Jin Kim; Korean J Pathol. 2010;44(6):597-604.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.597

4,556 View
33 Download
3 Crossref

Abstract PDF

BACKGROUND
At present, adequate prognostic markers for prostate cancer progression are still lacking, in spite of intensive investigation. Accordingly, our study examined the relationship between expression of candidate biomarkers and metastasis in prostate cancer patients. Correlation of molecular markers with prostate-specific antigen (PSA) level, Gleason sum score and tumor stage were also evaluated.
METHODS
A total of 105 prostate tumor specimens and specimens from 19 cases of nodular hyperplasia were obtained through Yeungnam University Hospital from 2007 to 2008. Immunohistochemical analyses for p16INK4a, phosphatase and tensin homolog (PTEN), E-cadherin, Ki-67 and Bcl-2 were performed.
RESULTS
Overexpression of Bcl-2 was significantly related to bone (p = 0.006) and nodal metastases (p = 0.017). Other biomarkers were not related to metastatic potential. There were statistically significant relationships between increased PSA level and loss of expression of PTEN (p = 0.019) and E-cadherin (p = 0.001). High Ki-67 index was significantly correlated with nodal metastasis (p = 0.029) as well as with loss of p16INK4a expression (p = 0.002) and high Gleason score (p = 0.011).
CONCLUSIONS
High Gleason score, Bcl-2 overexpression and increased Ki-67 labeling have significant predictive value in assessing the potential for prostate cancer metastasis. In addition, a high Ki-67 index is related to high Gleason score and loss of p16INK4a expression.

Citations

Citations to this article as recorded by

Over-expression of β-catenin is associated with high grade of prostatic cancer in Libyan patients
W. Said, F. Emaetig, K. El Gehani, T. Eldarat, A. Buhmeida, N. Enattah, A. Elzagheid, O. Al-Fituri
African Journal of Urology.2017; 23(2): 133. CrossRef
Bcl2 en cáncer avanzado de próstata y asociación con resistencia a la castración
R.F. Velázquez-Macías, F.E. De La Torre-Rendón, G. Ramos-Rodríguez, C.A. Calzada-Mendoza, R.M. Coral-Vázquez
Revista Mexicana de Urología.2016; 76(5): 288. CrossRef
Hedgehog signaling protein expression and its association with prognostic parameters in prostate cancer: A retrospective study from the view point of new 2010 anatomic stage/prognostic groups
Tae‐Jung Kim, Ji Youl Lee, Tae‐Kon Hwang, Chang Suk Kang, Yeong‐Jin Choi
Journal of Surgical Oncology.2011; 104(5): 472. CrossRef

Expression of P-glycoprotein and Apoptosis in Diffuse Large B-cell Lymphoma.: Ji Eun Kim, Young A Kim, Mee Soo Chang, Yunkyeong Jeon, JinHo Paik, Seon Og Yoon; Korean J Pathol. 2009;43(4):317-320.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.317

3,886 View
74 Download

Abstract PDF: BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma which responds well to conventional chemotherapy. However, quite a few patients have a recurrence with more aggressive forms after completion of therapy. Multidrug resistance proteins (MRP) are related to this process in several ways such as cell cycle alteration and modulation of apoptosis. METHODS: We investigated the expression of P-glycoprotein (Gp), one of the well-known MRP, as well as apoptosis associated proteins in DLBCL. Immunohistochemical staining for Gp, p53, Bcl-2, Ki-67, active caspase 3 and FADD was done in forty DLBCL cases. The association between MRP and apoptosis associated proteins to clinical findings was also tested. RESULTS: Twenty-nine patients out of 40 (73%) with DLBCL were positive for Gp, and 26 cases (65%) had a strong positive for Gp. Gp expression was stronger in high-grade lesions than in low-grade lesions and was associated to Bcl-2 expression. However, we could not find an adverse impact of Gp expression on patients' overall survival or relapse free survival rate. CONCLUSIONS: Our study revealed a high frequency of expression for Gp in DLBCL with a possible relationship between the expressions of Gp to apoptosis associated proteins.

Immunolocalization of the Apoptotic Inhibiting Protein (bcl-2) in Early Normal Pregnancy and Abortion.: Jiae Lee, Jeong Wook Kim, Bum Chae Choi, Kwang Moon Yang, Young Youl Cho, Sung Ran Hong; Korean J Pathol. 2001;35(1):48-52.

1,973 View
15 Download

Abstract PDF: BACKGROUND
The human placenta is an important organ in the maintenance of pregnancy, having functions in maturation and differentiation until the end of pregnancy. The bcl-2 protein is a proto-oncogene that prevents apoptosis and maintains cell survival. However, the mechanism through which bcl-2 inhibits apoptosis is unclear. The aims of this study are to localize bcl-2 at the placenta and to determine whether the expression of bcl-2 in early normal pregnancy is different from that of a missed abortion.
METHODS
Immunohistochemistry was performed for bcl-2 in formalin-fixed chorionic villi and decidual tissue collected from five early normal pregnancies and eleven missed abortions having histories of recurrent abortions during the first trimester.
RESULTS
The bcl-2 protein was observed in the syncytiotrophoblasts of chorionic villi and decidua in both the normal pregnancy and the missed abortion, and the expression of bcl-2 significantly increased in the missed abortion group (p<0.05).
CONCLUSION
The bcl-2 may be necessary to maintain pregnancy through modulating the survival of the syncytiotrophoblast and decidua without affecting cell proliferation, and the increased bcl-2 expression is presumed to be a reparative process to the increased apoptotic activity.

bcl-2 and p53 Protein Expression in Multiple Myeloma and Non-tumorous Plasma Cells A study related to survival.: Yu Na Kang, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Young Jae Lee; Korean J Pathol. 1999;33(3):179-186.

2,925 View
40 Download

Abstract PDF: The gene product of bcl-2 (B-cell leukemia/lymphoma-2) was suggested to suppress programmed cell death (apoptosis) of tumor cells and be involved in the development of multiple myeloma. However, the normal plasma cells also express the protein. It is unclear whether the expression of bcl-2 in multiple myeloma is of normal character or of regulatory adaptation in association with neoplastic transformation. p53 was also suggested to be involved in tumor progression since mutations on p53 were found in multiple myeloma. In order to find the relationship between the expression patterns of bcl-2 and p53 in tumor cells of multiple myeloma and non-neoplastic plasma cells, we examined 38 cases of multiple myeloma and 10 cases of nasal polyp immunohistochemically. Furthermore, expression of bcl-2 and p53, mitosis, clinical stage and infiltrative pattern of tumor cells in bone marrow were also evaluated in association with the survival of patients. By immunostaining with anti-bcl-2 and p53 monoclonal antibody, 37 out of 38 cases of multiple myeloma and all of 10 cases of nasal polyp were positive for bcl-2 but only 7 cases of multiple myeloma were positive for p53. Marked dysplasia, low percentage of bcl-2 expression, and increased mitoses were correlated with poor prognosis. Based on these observations, we suggest that bcl-2 and p53 are involved in tumorigenesis of multiple myeloma and the survival of patients would be influenced by dysplastic change, mitosis and degree of bcl-2 expression.

Expression of bcl-2 Protein in Colorectal Adenoma and Adenocarcinoma and its Relationship with p53 and Apoptosis.: Ae Ree Kim, Seong Jin Cho, Nam Hee Won, Yang Seok Chae; Korean J Pathol. 1997;31(5):417-426.

1,932 View
17 Download

Abstract PDF: Either increased cellular proliferation or decreased death might result in an expansion of their numbers in the oncogenic process. Cellular apoptosis represents an autonomous suicide pathway that helps to restrict the cell number. However bcl-2 and mutant p53 inhibit programmed cell death. To determine whether the bcl-2 gene is activated during colorectal tumorigenesis and whether it has any relationship with p53 and apoptosis, we studied the expression of bcl-2 and p53 in the normal colonic mucosa, in the adenomatous polyps and in the adenocarcinomas using the immunohistochemical method. Also we evaluated the status of apoptosis using the in situ end labeling method. The bcl-2 immunoreactivity was restricted to the basal epithelial cells of all normal colonic mucosa and they were expressed in all adenomas and 86% of adenocarcinomas, especially in the superficial lesion of some tumors. Mutations of p53 were not found in the normal colonic mucosa, but they were present in dysplastic cells of adenomas (52%) and in cancer cells of the adenocarcinomas (47%). Apoptosis was confined to the tips of the normal colonic mucosa. It was more easily detected in the p53-positive adenomas than in the p53-negative adenomas (p=0.010). In the adenocarcinomas, the findings of apoptotic process are not related with p53 mutation (p=0.3) and bcl-2 expression (p=0.187). p53 and bcl-2 are probably one step of several apoptotic processes in the adenocarcinomas.

Histopathologic Re-evaluation of Thymoma with Immunonhistochemical Study for bcl-2 and MIC-2 Protein.: Kyung Moo Yang, Mee Yon Cho, Soon Won Hong, Tae Seung Kim, Chan Il Park, Woo Ick Yang; Korean J Pathol. 1997;31(5):446-461.

2,115 View
26 Download

Abstract PDF: We reviewed 86 thymic epithelial tumors and reclassified them according to the Kirchner and Muller- Hermelink classification. They were subtyped as medullary, mixed, predominantly cortical (organoid), cortical, well differentiated thymic carcinoma, and poorly differentiated thymic carcinoma. The frequency of each subtype was determined and histologic findings were related to stage and myasthenia gravis. Immunohistochemical stains for bcl-2 protein as a marker for medullary thymocytes and MIC-2 protein as a marker for cortical thymocytes were performed in each case. The stages and association of myasthenia gravis was significantly different in each subtypes. The results of this study demonstrate that this histogenetic classification is clinically applicable. The bcl-2 protein was specifically demonstrated in lymphocytes within areas of medullary differentiation and MIC-2 protein in cortical differentiation. The expression of bcl-2 and MIC-2 proteins lend histogenetic support for this new classification of thymoma. Bcl-2 protein is strongly expressed in tumor epithelial cells of every case of poorly differentiated thymic carcinoma whereas the other types of thymic epithelial tumors do not show epithelial expression of this protein. The strong expression of bcl-2 protein in tumor epithelium may be considered as a predictor of aggressive behavior in thymic epithelial tumors.

Morphohistometric Investigation and bcl-2 Expression in the Placenta of Chromosomally Abnormal Pregnancy.: Joung ho Han, Kyu Rae Kim, Yeon Lim Suh, Mi Kyung Kim, Young Hyeh Ko, Dae Shick Kim, Howe Jung Ree; Korean J Pathol. 1999;33(5):353-360.

2,103 View
21 Download

Abstract PDF: To evaluate the significance of placental histology, a collaborative histological and cytogenetic study was performed on the products of 88 spontaneous abortions, and subsequently bcl-2 immunostaining was performed on 62 cases. The morphometric parameters included were DCIRCLE, FORMSHAPE, CPRATIO, and the expression of bcl-2 immunostainig was graded in four categories (I to IV). The results were as follows: 1) 40% (n=35) were chromosomally abnormal: trisomies predominated (57%, n=20) and was followed by triploidy (14%, n=5), double trisomy (6%, n=2), monosomy X (6%, n=2), inversion (9) (6%, n=2). 2) mean of DCIRCLE in chromosomally abnormal pregnancy was 40 micrometer larger than that in chromosomally normal pregnancy (p=0.012, one side t-test), while no difference was found in FORMSHAPE and CPRATIO between chromosomally abnormal and normal pregnancy. 3) bcl-2 expression was found in syncytiotrophoblast and cytotrophoblast. bcl-2 expression was weaker in chromosomally abnormal pregnancy with intensity I and II of 59% than chromosomally normal pregnancy with intensity I and II of 24%. 4) In comparison bcl-2 expression with DCIRCLE, in chromosomally normal abortion one (10%) in I & II and one (3%) in III & IV showed large DCIRCLE (above 360 micrometer), while 11 (85%) in I & II and 3 (33%) in III & IV in chromosomally abnormal pregnancy. It would mean that bcl-2 protein is necessary in preservation of pregnancy and placental morphology. Abnormal villous diameter and weak bcl-2 expression may be suggestive of chromosomal anomaly. Besides other histologic parameters, application of bcl-2 immunostaining and morphometric analysis probably give more sensitive and specific results in identifying chromosomally abnormal abortion.

Expression Patterns of Bcl-2 and PCNA in Cervical Intraepithelial Neoplasia.: Mee Sook Roh, Gi Yeung Huh, Sook Hee Hong; Korean J Pathol. 1995;29(6):703-713.

1,986 View
12 Download

Abstract PDF: Immunohistochemical stains for bcl-2 oncoprotein and PCNA and examination of the mitosis level were perfon-ned in 76 cases of cervical intraepithelial neoplasia (CIN). We studied the expression pattern of bcl-2 protein according to histologic grades and the function of bcl-2 oncogene associated with cellular proliferation by comparing with PCNA expression and the mitosis level. The results were as follows: 1) Of 76 cervical intraepithelial neoplasias, 23 (30.3%) were CIN I, 23 (30.3%) were CIN II, and 30 (39.4%) were CIN III. 2) Of 23 CIN I cases, grade 0 and 1 mitosis level were seen in 20 (87.0%), PCNA in 16 (69.6%), and bcl-2 in 19 (82.6%) cases, respectively, which indicates that CIN I lesions have a low cellular proliferative activity. 3) Of 30 CIN III cases, grade 2 and 3 mitosis level were noted in 28 (93.3%), PCNA in 25 (83.3%) and bcl-2 in 19 (63.3%) cases, respectively, which indicates that CIN III lesions have a high cellular proliferative activity. The results suggest that progressive increase of dysfunctional proliferative activity and abnormal decrease of cell death result in increased number of neoplastic cells according to CIN grade. Also the expression rate of bcl-2, PCNA and mitosis level were significantly different between CIN I and 111, which suggest that they might be good parameters for classifying CIN into low and high grade and for prediction of the biologic behavior of the CIN lesion.

Microvessel Density and Expressions of bcl-2, p53, and Vascular Endothelial Growth Factor in Endometrial Carcinoma.: Soon Young Kim, Hae Jin Jeong, Myeng Sun Park, Bang Hur; Korean J Pathol. 2001;35(5):401-407.

1,978 View
14 Download

Abstract PDF: BACKGROUND
Recent studies have shown that oncogenes and tumor suppressor genes are involved in tumorigenesis and tumor progression. The inverse role of bcl-2 and p53 in endometrial carcinomas has been debated. Moreover, their roles in angiogenesis as well as the interrelationship between prognostic clinico-pathological factors and angiogenesis have not been elucidated in endometrial carcinomas.
METHODS
The expression rates of bcl-2, p53 and vascular endothelial growth factor (VEGF) in thirty-eight cases of surgically removed endometrial carcinomas were investigated using an avidin-biotin complex method of immunohistochemistry. CD34 immunostain for microvessel density (MVD) was also performed.
RESULTS
The expression rate of bcl-2 was higher in the endometrioid type carcinoma (43.8%) than in the non-endometriod type carcinoma (16.7%). There was a significantly increased bcl-2 expression in grade I compared to grades II and III (P<0.05). The p53 expression rate was significantly higher in the non-endometriod type carcinoma than in the endometrioid type carcinoma (P<0.05).The VEGF expression rate was higher in the non-endometriod type carcinoma (83.3%) than in the endometrioid carcinoma (28.1%). Differences of MVD according to stages, histological types, grades and bcl-2, p53 and VEGF expressions were not noted.
CONCLUSIONS
The expression rate of bcl-2 increases in the low grade endometrial carcinoma more than in the high grade one, so it may be suggested that bcl-2 expression could be used for an ancillary prognosticator. However, p53 and VEGF expressions and microvessel density may not have any prognostic value.

Expression of Epstein-Barr Virus Gene Products, Bcl-2 and p53 Proteins in Nasopharyngeal Carcinomas.: Sun Hee Yoon, Kang Suek Suh, Chang Hun Lee; Korean J Pathol. 1997;31(8):723-734.

1,969 View
16 Download

Abstract PDF: The authors studied EBV genome expression in 40 conventionally processed samples of nasopharyngeal carcinomas (NPC), using in situ hybridization for EBERs and immunohistochemistry for LMP, Bcl-2 and p53 proteins. The NPCs consisted of 6 keratinizing squamous cell carcinomas (KSCs), 13 nonkeratinizing carcinomas (NKCs) and 21 undifferentiated carcinomas (UCs). The results were summarized as follows: 1) EBERs were expressed in 80.0% of all the NPCs (32/40). As for the subtypes, they were detected in 92.3% of NKCs (12/13), in 90.5% of the UCs (19/21), and in 16.7% of the KSCs (1/6). In positive cases, the nuclei of tumor cells displayed uniformly strong staining. 2) LMP was expressed in 10.0% of all the NPCs (4/40), all of which were UC. The LMP expression in the UCs was not correlated to the expression of EBERs, Bcl-2 and p53 proteins. 3) Bcl-2 protein was detected in 85.0% of all the NPCs (34/40). As for the subtypes, they were detected in 92.3% of the NKCs (12/13), in 90.5% of the UCs (19/21), and in 50.0% of the KSCs (3/6). 4) p53 protein was detected in 75.0% of all the NPCs (30/40). As for the subtypes, they were detected in 81.0% of the UCs (17/21), in 69.2% of the NKCs (9/13), and in 66.7% of the KSCs (4/6). 5) In the NPCs the expression of EBER showed a significantly positive correlation with that of p53 or Bcl-2 protein. The above results indicate that the association of EBV with NPC is chiefly with poorly differentiated and undifferentiated carcinomas. Additionally, carcinomas commonly display widespread, strong immunoreactivity of Bcl-2 and p53 proteins over tumor cells. In conclusion, these observations indicate that the EBV-association in NPC appears to contribute to the overexpression of tumor-related genes during carcinogenesis.

Expression of bcl-2, p53 and VEGF in Non-Small Cell Lung Carcinomas: Their Relation with the Microvascular Density and Prognosis.: Jinyoung Yoo, Ji Han Jung, Hyun Joo Choi, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2005;39(2):74-80.

2,164 View
20 Download

Abstract PDF: BACKGROUND
The aim of this study was to investigate the expression of bcl-2, p53 and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC), and to examine the relationship between those protein expressions and neovascularization. We also analyzed the prognostic impact of these biological parameters on the patients' overall survival rate.
METHODS
The archival tumor tissues from 147 previously untreated patients with NSCLC were examined by immunohistochemistry for bcl-2, p53 and VEGF proteins. The vascularity was measured by the average microvascular density (MVD) of the CD34-positive vessels. Clinical information was obtained through the computerized retrospective database from the tumor registry.
RESULTS
Immunoreactivity for bcl-2 was detected in 17% (25/147), p53 in 72% (106/147) and VEGF in 75% (110/147) of the tumors. An inverse association was found between bcl-2 expression and VEGF expression (p=0.012). There was a significant correlation between the bcl-2 expression and the MVD (p=0.009), and also between the p53 expression and the MVD (p=0.045). The mean survival time was associated with the patients' age (p=0.032), the T status (p=0.038), the tumor stage (p=0.009), and expressions of bcl-2 (p=0.016) and VEGF (p=0.039). On multivariate analysis, only the tumor stage and VEGF expression maintained their prognostic influence.
CONCLUSIONS
Our data suggest that bcl-2 and p53 alterations are involved in the angiogenesis of NSCLC, and are either dependent on or independent of VEGF. It is further noteworthy that the tumor stage and VEGF expression may be useful in predicting patients' survival.

Expression of p63,bcl-2,bcl-6 and p16 in Basal Cell Carcinoma and Squamous Cell Carcinoma of the Skin.: Zhenlong Zheng, Youngchul Kye, Xianglan Zhang, Aeree Kim, Insun Kim; Korean J Pathol. 2005;39(2):91-98.

2,515 View
34 Download

Abstract PDF: BACKGROUND
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the common malignant neoplasms of the skin. The p63 is a p53 homologue which is considered to be a reliable keratinocyte stem cell marker. Bcl-2 plays a key role in cell longevity by preventing apoptosis, whereas the bcl-6 gene functions as a transcriptional repressor. The p16-CDK4/6 complex arrests the cell cycle at G0 /G1 phase. In the present study, the expression of p63, bcl-2, bcl-6, and p16 in BCC and SCC was evaluated.
METHODS
Forty-seven BCCs and 43 SCCs were selected and microarrayed in paraffin blocks. Immunohistochemical analysis was performed with specific antibodies for bcl-2, bcl-6, p16 and p63.
RESULTS
p63 was found to be expressed in all BCCs and SCCs. Bcl-2 was exclusively expressed in BCCs (100%), but there was negative expression in SCCs, whereas bcl-6 was positively expressed in 18.2% of SCCs, and was negative in BCCs. In SCCs, p16 was expressed at high frequency (47.7%) than in BCCs (14.9%). The expression of p16 was correlated with the histologic grades of SCCs.
CONCLUSION
The different patterns of bcl-2, bcl-6, p63 and p16 protein expression between BCCs and SCCs may represent the different histogenesis and morphologic features of two lesions.

Immunohistochemical Study on the Expression of p53 and Bcl-2 Proteins in Non-Small Cell Lung Carcinomas.: Ok Ju Lee, Do Youn Park, Kang Suek Suh; Korean J Pathol. 1997;31(9):823-831.

1,978 View
17 Download

Abstract PDF: To address the possible prognostic value of p53 and Bcl-2 proteins in non-small cell lung carcinomas (NSCLCs), the authors studied 43 cases of NSCLCs diagnosed between the years 1990 to 1995 at Pusan National University Hospital. The patients were treated either by pneumonectomy or lobectomy of the lung. The expression of p53 and Bcl-2 proteins was semiquantitatively analyzed in paraffin sections by immunohistochemical method and correlated with clinicopathologic prognostic parameters of NSCLCs. Overexpression of the p53 protein was found in 31 cases (72.1%) of the 43 NSCLCs. Overexpression of the p53 protein was significantly correlated with the decreasing degree of histologic differentiation, increasing tumor stage, and cigarette smoking. Bcl-2 expression was found in 19 cases (44.2%) of the 43 NSCLCs. Increased expression of the Bcl-2 protein was significantly correlated only with decreasing tumor stage. An inverse relationship was found between p53 and Bcl-2 proteins, but it was not statistically significant. Thus p53 and Bcl-2 proteins, as demonstrated immunohistochemically in routine paraffin sections, could be of value in prediction of the aggressiveness and prognosis of NSCLCs, in agreement with the central role of p53 and Bcl-2 proteins in the evolution of NSCLCs associated with cigarette smoking.

The Studies of bcl-2 Oncoprotein and Epstein-Barr Virus Expression in Malignant Lymphomas: Immunohistochemical and in situ hybridization analysis on 66 cases.: Hye Jae Cho, Yeon Mee Kim, Hyun Ju Yoo, Jong Eun Joo; Korean J Pathol. 1996;30(2):121-131.

2,003 View
12 Download

Abstract PDF: Bcl-2 oncoprotein is being localized to mitochondria and interfering with programmed cell death (apoptosis) independent of promoting cell division in the lymphoid and nonlymphoid cells. The bcl-2 oncoprotein expression has been reported in follicular lymphomas as well as in diffuse non-Hodgkin's lymphoma, leukemia and a variable propotion of Hodgkin's lymphoma cases. Recent evidence suggests that some lymphomas protected from apoptosis is conferred through expression of Epstein-Barr virus(EBV) latent membrane protein which turn to cause upregulation of bcl-2. To define the role of the bcl-2 oncoprotein and EBV in lymphoid malignancy, we tried immunohistochemical studies with anti-bcl-2 antibody and In situ hybridization (ISH) with EBV-encoded small nuclear RNAs(EBER) in the paraffin embedded sections of 46 non-Hodgkin's lymphoma (NHL) cases and 20 Hodgkin's lymphoma (HL) cases. Bcl-2 oncoprotein expression was found in 37 of 46 cases (80%) of NHL with relatively strong cytoplasmic staining, and in 14 of 20 cases (70%) of HL with weak cytoplasmic staining in limited small numbers of RS, Hodgkin and lacunar cells. The widespread presence of bcl-2 oncogene in many different types of both NHL and HL supports that the extended cell survival through overexpression of bcl-2 gene protein may be a growth advantage of neoplastic lymphoid cells. In the ISH analysis for EBV, the presence of EBV was detected in 17 of 20 cases (85%) of HL, compared to 6 of 44 cases(13.6%) of NHL. It appears to be no direct correlation between overexpression of bcl-2 oncoprotein by neoplastic lymphoid cells and the presence of EBV in NHL but it seems to be a definite association between EBV and HL.

Mutational Analysis of Proapoptotic bcl-2 Family genes in Colon Carcinomas.: Young Hwa Soung, Jong Woo Lee, Su Young Kim, Suk Woo Nam, Won Sang Park, Jung Young Lee, Nam Jin Yoo, Sug Hyung Lee; Korean J Pathol. 2005;39(3):168-171.

2,038 View
29 Download

Abstract PDF: BACKGROUND
Several lines of evidence have indicated that the deregulation of apoptosis is involved in the mechanisms of cancer development, and somatic mutations of the apoptosisrelated genes have been reported in human cancers. Members of the bcl-2 family proteins regulate the intrinsic apoptosis pathway mainly in the mitochondria. The aim of this study was to explore whether the somatic mutation of the proapoptotic bcl-2 family genes, one of the mechanisms that prolong the survival of cancer cells, occurred in colorectal carcinomas.
METHODS
In the current study, to detect the somatic mutations in the DNA sequences encoding the bcl-2 homology 3 (BH3) domain of the human bak, bid, bik, bim, PUMA, bcl-rambo, bcl-G, and bmf genes in 98 colon adenocarcinomas, we used polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), and DNA sequencing.
RESULTS
The SSCP analysis detected no evidence of somatic mutations of the genes in the coding regions of the BH3 domain in the cancers.
CONCLUSIONS
The data presented here indicate that the proapoptotic bcl-2 family genes, bak, bid, bik, bim, PUMA, bcl-rambo, bcl-G and bmf may not be somatically mutated in human colorectal carcinomas, and suggest that the colorectal cancers may not utilize mutational events of these proapoptotic bcl-2 family genes in the mechanisms for evading apoptosis.

Expression of Apoptosis, bcl-2, and PCNA in Uterine Cervical Intraepithelial Neoplasia and Invasive Carcinoma.: Myoung Ja Chung, Kyu Yun Jang, Myoung Jae Kang, Dong Geen Lee, Byung Chan Oh; Korean J Pathol. 1997;31(11):1180-1189.

2,266 View
10 Download

Abstract: This study was undertaken to know the extent of apoptosis, expression of bcl-2 and proliferating cell nuclear antigen (PCNA) in uterine cervical intraepithelial neoplasia (CIN; 15 cases) and invasive carcinoma (27 cases) and to evaluate them as a prognostic marker. Apoptosis was analysed by using the in situ apoptosis detection kit and bcl-2 and PCNA were detected by the immunohistochemical method. The results were as follows: Apoptotic indices (AI) in the invasive carcinoma (mean: 4.3) were 10-times higher than that in the CIN (mean: 0.43). Bcl-2 was expressed 60% of the cases in the dysplastic cells of the CIN II and CIN III, 33.3% of cases in the invasive carcinoma and not expressed in the CIN I except basal cells. The expression of the PCNA was increased by the grades of CIN and was strong in invasive carcinoma. The mean survival time of the patient with invasive carcinoma was significantly decreased in the higher AI index (above 4.3) than in the lower AI index (below 4.3). There was no significant correlation between the extent of apoptosis and the expression of bcl-2. According to the above results, AI are able to be used as an independent prognostic marker in the invasive cervical carcinoma, and bcl-2 and PCNA have an important role in the tumorigenesis of uterine cervical carcinoma.

Relationship between HPV Infection and bcl-2 Protein Expression and Apoptosis in Invasive and In Situ Squamous Cell Carcinoma of the Uterine Cervix.: Myoung Ja Chung, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee; Korean J Pathol. 1999;33(9):702-708.

2,294 View
24 Download

Abstract PDF: Human papillomavirus (HPV) 16/18 is a causative agent of uterine cervical carcinoma. HPV 16/18 can alter cell cycle regulation through apoptosis. Bcl-2 is an important regulatory gene of apoptosis. A study was done to evaluate the relation between HPV 16/18 and bcl-2 and apoptosis in 21 cases of carcinoma in-situ (CIS), 5 cases of microinvasive carcinoma and 23 cases of invasive squamous cell carcinoma. HPV 16/18 was detected by hybrid capture system (HCS), bcl-2 protein by immunohistochemical method and apoptosis by using the hematoxylin-eosin stained slide. The results were as follows: Expression of the bcl-2 protein was 43% (9/21) in CIS and 26% (6/23) in invasive carcinoma. Expression of the bcl-2 protein was 42% (5/12) in CIS with HPV 16/18 infection, 44% in CIS without HPV 16/18 infection, 20% (2/10) in invasive carcinoma with HPV 16/18 infection and 31% (4/13) in invasive carcinoma without HPV 16/18 infection. Mean apoptotic index (mAI) was 3.36 in CIS, 5.23 in microinvasive and 6.25 in invasive carcinoma. mAI was 3.66 in CIS with HPV 16/18 infection, 2.86 in CIS without HPV 16/18 infection, 6.18 in invasive carcinoma with HPV 16/18 infection and 6.30 in invasive carcinoma without HPV 16/18 infection. Based on these results, we conclude that there are no correlation between HPV infection and bcl-2, and between HPV infection and apoptosis in invasive and in situ carcinoma of the uterine cervix, and apoptosis is increased according to tumor progression.

Correlation of Ki-67, p53 and bcl-2 Expression with Grade and Behavior of Ependymoma.: Jae Ho Han, Tai Seung Kim; Korean J Pathol. 1999;33(9):723-728.

2,442 View
28 Download

Abstract PDF: Ependymomas constitute no more than 5 to 7% of all primary CNS neoplasm and their biologic behavior is difficult to predict by microscopic appearances. Recently, many studies have attempted to correlate biologic behavior with tumor proliferation index, tumor suppressor gene and oncogene using immunohistochemical stains. We evaluated 25 cases of surgically resected intracranial ependymomas for the proliferation activity using Ki-67, and expression of p53 and bcl-2 protein with regard to the prognosis. The cases were divided into 17 ependymomas (WHO Grade II), 3 papillary ependymomas (WHO Grade II), and 5 anaplastic ependymomas. Clinically, the patients were divided into two groups, recurrent (18 cases) or non-recurrent (7 cases). The Ki-67 proliferation index was significantly higher in the recurrent group (p<0.05) and in the younger ages (correlation index=0.534). Although Ki-67 proliferation index was higher in anaplastic ependymoma, it was not significant statistically (p>0.05). p53 protein expression tended to increase in the patients who had anaplastic ependymoma and in the recurrent group. bcl-2 expression was not correlated with histologic grade or recurrence of the tumor. We conclude that Ki-67 proliferation index and p53 expression are important markers for predicting biologic behavior of ependymoma.

An Analysis of p53, bcl-2 and Ki-67 Expressions, and Apoptosis in Rectal Cancer: Their Correlation with the Tumor Response after Preoperative Radiochemotherapy.: Jinyoung Yoo, Su Zy Kim, Hyeon Min Cho, Sung Whan Kim, Hyung Min Chin, Jung Yong Lee, Jun Ki Kim, Seok Jin Kang, Chung Soo Chun, Chang Suk Kang; Korean J Pathol. 2005;39(4):222-228.

2,117 View
22 Download

Abstract PDF: Background
: Preoperative radiochemotherapy (RCT) has been administered for locally advanced rectal cancer to increase the therapeutic benefits, and to preserve the sphincter in low-lying tumors, however, tumor responses after RCT are variable. Methods : Apoptotic index (AI), and expressions of Ki-67, p53 and bcl-2 were analyzed in pretreatment biopsies from 69 patients with rectal cancer by immunohistochemistry. Tumor response was graded in surgically resected specimens by using a three-scale grading system: no response (NR), partial remission (PR) and complete remission (CR). Results : CR was identified in 19 cases (28%), PR in 24 cases (35%), and NR in 26 cases (38%) of 69 cases. p53 protein was expressed in 49 cases (71%), whereas bcl-2 was in 42 cases (61%). The pretreatment Ki-67 labeling index was 65.4+/-3.4%. The tumor response was not associated with any of these markers. Tumors with CR/PR showed a higher AI (0.84+/-.84%/0.66+/-.52%) than that of tumors with NR (0.58+/-0.54%). There was a significant correlation between tumor response and the histologic differentiation (p=0.008) or recurrence (p=0.039). Conclusions : The AI revealed a tendency to increase in tumors with CR/PR, while expressions of p53 and bcl-2, and Ki-67 labeling index had little direct association with tumor response.

Immunohistochemical Study on the Expression of Bcl-2 and p53 Protein in Gastric Adenocarcinoma.: Joon Hyuk Choi, Won Hee Choi; Korean J Pathol. 1997;31(12):1282-1290.

2,075 View
17 Download

Abstract PDF: This study was carried out to investigate the immunohistochemical expression of bcl-2 and p53 protein in the intestinal type and the diffuse type of gastric adenocarcinoma by Lauren's classification. A total of 100 cases, including 50 cases of the intestinal type and 50 cases of the diffuse type from paraffin embedded gastrectomy specimens, were immunohistochemically stained for bcl-2 and p53 protein. Bcl-2 protein was expressed in 38% (19/50) of intestinal type and 30% (15/50) of diffuse type. The incidence of bcl-2 protein expression was higher in the intestinal type than in the diffuse type, but no significant correlation was present (p>0.05). p53 protein was expressed in 68% (34/50) of the intestinal type and 60% (30/50) of the diffuse type. The incidence of p53 protein expression was higher in the intestinal type than in the diffuse type, but no significant correlation was present (p>0.05). And an expression of bcl-2 and p53 protein did not correlate with depth of invasion, lymph node meatastasis and TNM stage, respectively (p>0.05). These results suggest that bcl-2 and p53 gene alteration appear to play a more important role in the carcinogenesis of the intestinal type than the diffuse type. However, there is no significant difference between the intestinaPU: The Korean Society of Pathologistsl type and the diffuse type in bcl-2 and p53 protein expression.

Taxol-induced Pathological Findings in Rat Small Intestine.: Sun Hee Chang, Shi Nae Lee, Hee Soo Yoon, Min Sun Cho, Hea Soo Koo, Woon Sup Han; Korean J Pathol. 1997;31(12):1291-1296.

2,186 View
14 Download

Abstract PDF: Taxol is an active chemotherapeutic agent against a variety of solid tumors and a potentially useful drug for augmenting the cytotoxic action of radiotherapy against certain cancers. Taxol blocks cells in the mitotic phase of cell cycle. The aim of this study was to define the in vivo response of rapidly dividing cells of the small intestinal mucosa to taxol. We studied the numbers of apoptotic and mitotic cells and the expression of bcl-2 and p53 in rat jejunal crypt cells at 1, 2, 4, 8, 12, 16, and 24 hours and 3 and 5 days after intraperitoneal injection of taxol. Mitosis peaked at 2 and 4 hours and 12 and 16 hours. Apoptosis peaked at 16 hours and returned to normal after five days. The glands in crypts showed marked distortion with atypical lining cells after three days, which returned to normal at 5 days. bcl-2 expression was markedly decreased at 8 to 24 hours and subnormally recovered after three to five days. p53 showed no significant changes throughout. The histopathological changes in small intestine due to taxol were transient with complete recovery. bcl-2 expression was inversely corresponded to numbers of apoptosis. The changes were p53 independent. Further studies to understand the conditions that maximize the cell-cycle modulating effects of taxol cl-may greatly enhance its anti-tumor effectiveness.

Correlation of Clinical Stage and Presumptive Prognostic Factors in Renal Cell Carcinoma.: Jin Ye Yoo, Hye Jae Cho; Korean J Pathol. 1999;33(11):1061-1066.

1,961 View
16 Download

Abstract PDF: Renal cell carcinoma is the most common primary cancer of the kidney. The tumor stage is a reliable prognostic marker in renal cell carcinoma which is significantly associated with patient survival. But assessment of other prognostic factors has produced varying and often conflicting results. We reevaluated the significance of varied prognostic parameters in 33 cases of renal cell carcinoma; clinical stage, cell type, histologic pattern, DNA ploidy, Ki-67 labeling index, and bcl-2 oncoprotein expression. We could not statistically prove that DNA ploidy and bcl-2 expression were related to any examined parameters. Cell type was not related to clinical stage nor nuclear grade but there was a significant correlation (p=0.002) between cell type and histologic pattern. Nuclear grade (p=0.007) and Ki-67 labeling index (p=0.036) were significantly related to clinical stage, suggesting their value as complementary prognostic markers for renal cell carcinoma.

A Study of Bcl-2 Oncoprotein Expression in Endometrial Carcinoma Correlated with Hormone Receptor Status.: Young Im Han, Hye Jin Lee, Ji Yeon Lee, Sun Kyung Lee; Korean J Pathol. 1996;30(5):408-416.

1,977 View
18 Download

Abstract PDF: Bcl-2 is a proto-oncogene initially described in follicular lymphoma, associated with chromosomal translocation(14;18). Recent studies have shown the presence of Bcl-2 in nonhematolymphoid tissue, especially in hormonally responsive tissue. The endometrium is an attractive model for studying the hormone dependent regulation of Bcl-2 expression. We have studied the immunoreactivity of Bcl-2 oncoprotein in relation to the immunoreactivity of estrogen receptors(ER) and progesterone receptors(PR) by immunohistochemistry in 52 human endometrial carcinomas, according to nuclear grade. The results obtained are summarized as followings, 1) Immunohistochemical grade of Bcl-2 showed a significant inverse correlation with nuclear grade. 2) Immunohistochemical grades of ER and PR also showed a significant inverse correlation with nuclear grade, and were well correlated with each other. 3) Immunohistochemical grades of Bcl-2 and hormone receptors showed a strongly significant correlation. On the basis of the above results, we suggest that Bcl-2 expression may be under hormone dependent control and that it can be used in prognosis and choice of hormonal therapy in the presence of hormone receptor.

Detection of bcl-2/IgH Gene Rearrangement and Expression of c-myc and p53 Oncoprotein in B-cell Lymphoma.: Ghee Young Kwon, Chul Woo Kim; Korean J Pathol. 1996;30(5):437-446.

2,088 View
25 Download

Abstract PDF: Many kinds of genetic changes have been known to be associated with malignant lymphoma and bcl-2, p53 and c-myc are some examples. We investigated the expression of p53 and c-myc protein in follicular and diffuse B cell lymphoma by immunohistochemistry to study the possible role of these proteins in the lymphomagenesis and transformation of the tumor. The rearrangement of bcl-2 oncogene and the immunoglobulin heavy chain gene was searched for in those cases by polymerase chain reaction(PCR). Paraffin-embedded tissues of fifteen follicular lymphomas and 14 diffuse lymphoma cases were used. The results of immunohistochemical staining are summarized as follows: 1) p53 positivity is significantly higher in diffuse lymphoma than in follicular lymphoma(P=0.001); 2) c-myc expression is not increased in diffuse lymphoma compared with follicular lymphoma; 3) PCNA index is significantly higher in diffuse lymphoma than in follicular lymphoma(P=0.03) but there was no statistically significant correlation between PCNA index and p53 positivity(P=0.44); 4) Eight out of 14 cases of follicular lymphoma and 12 of 14 cases of diffuse lymphoma showed rearrangement of the immunogloblulin heavy chain gene; 5) bcl-2 oncogene rearrangement was identified in only one case of follicular lymphoma and all the diffuse type lymphomas were negative in bcl-2/IgH rearrangement. In conclusion, assuming that the follicular pattern of B-cell lymphoma often transforms to diffuse type in later stages, c-myc over-expression might be an earlier event than p53 mutation in the process of tumor progression in B-cell lymphoma. bcl-2/IgH gene rearrangement in follicular lymphoma is a rare finding in Korea compared to that of Western countries.

Gender Differences in Expression of Apoptosis, p53, and Bcl-2 in Delayed Focal Cerebral Infarction in Rats.: Hee Suk Jung, Seung Won Park, Sung Nam Hwang, Young Bak Kim, Mi Kyung Kim, Byung Kuk Min, Jung Taik Kwon, Duck Young Choi, Jong Sik Suk; Korean J Pathol. 2000;34(1):1-10.

2,126 View
31 Download

Abstract PDF: Apoptosis is a normal physiological process. Morphological studies have shown that cells die by physiological mechanisms after undergoing characteristic changes termed 'apoptosis' or 'programmed cell death'. Several genes were known to participate in the apoptotic process including p53 as a proapoptic gene and Bcl-2 as an antiapoptic gene. It was also known that there are certain gender differences in the cerebrovascular accidents and their effect on tissue damage. The purpose of this study is to evaluate how the apoptotic genes are expressed in delayed focal cerebral infarction and peri-infarct area in male and female adult rats by comparing the immunoexpression of p53 and Bcl-2 and p53:Bcl-2 ratio at delayed focal cerebral infarction between both sexes. In sixteen adult Spraugue-Dawley rats (nine males and seven females), the right MCA and both CCA were ligated for thirty minutes to make a delayed focal cerebral infarction in right frontal lobe. Their brains were taken at seventy two hours after the operation. And then the brains were prepared for immunohistochemical stains for apoptosis, p53 and Bcl-2 proteins. The infarction volume of male rats (11.3 mm3) was larger than that of female rats (7.3 mm3) (p<0.01). In male group, the width (micrometer2) of the apoptotic area (46.4 micrometer2) was significantly larger than those in female group (38.9 micrometer2) (p<0.005). The p53 : Bcl-2 ratio was significantly higher in male group (3.23) compared with female group (2.18) (p<0.01). As a result, the p53:Bcl-2 ratio seemed to be related to the gender differences in neuronal apoptosis after delayed focal cerebral infarction.

Clinico-Pathologic Evaluation of 18 Cases of Lymphomatoid Papulosis.: Sug Kyoung Ko, Hye Sook Kim, Kee Suck Suh, Sang Tae Kim, Man Ha Huh; Korean J Pathol. 1996;30(6):505-514.

2,166 View
18 Download

Abstract PDF: Lymphomatoid papulosis is an enigmatic disease entity which is clinically benign and histologically malignant. Although sporadic cases have been reported, we could not find any comprehensive report on the combined clinical and histologic features of lymphomatoid papulosis in the literature. Perhaps the most controversial aspect of lymphomatoid papulosis is its pathogenesis and categorization as a benign versus a malignant entity. To date, there are no reports on p53 and bcl-2 protein expression in lymphomatoid papulosis. We analysed the clinico-pathological findings of 18 cases with lymphomatoid papulosis during the 10 year period from 1984 to 1995 and examined the prevalence of immunoreactivity for CD30(DAKO, Ber-H2), p53(DAKO, DO-7), and bcl-2(DAKO, 124) using an immunohistochemical(ABC) method. The results obtained are summarized as follows. 1) Age distribution ranged from 20 to 65, with a mean age of 45 years and a sex distribution which showed a male predominence(8:1). The lesions were located on the trunk and extremities(8cases), extremities (7cases), and trunk(3 cases). The morphology of the lesions were papules or plaques(12 cases), and nodules(6 cases). 2) Histopathologic types were classified into 3 types: type A(4 cases), type B(8 cases) and mixed type (6 cases). 3) Positive immunoreactivity for CD30 was seen in 17%(3 of 18cases): type A(2 of 3) and mixed type(1 of 3). 4) The positive immunoreactivity for p53 and bcl-2 was observed in 29%(5 of 18) and 11%(2 of 18), respectively. 5) Cases showing positive immunoreactivity for P53 were type A(1 of 5), type B(1 of 5), and mixed type(3 of 5). 6) Cases showing positive immunoreactivity for bcl-2 were mixed type(2 of 2). One case developed into Ki-1 lymphoma. These results support the idea that lymphomatoid papulosis and Ki-1 lymphoma represent a continuum. The role of p53 gene mutation and bcl-2 activation in the development of lymphomatoid papulosis is currently unknown. But, our results suggest that p53 gene mutation and bcl-2 activation are not a critical step in the development of lymphomatoid papulosis. Further studies are needed to elucidate the role of p53 gene mutation and bcl-2 activation in the development and progression of lymphomatoid papulosis.

Histopathologic Findings & Expression of bcl-2 of the Endometrium Analysis of 1,000 consecutive biopsies of uterine bleeding .: Hye Kyung Lee, Dong Geun Lee, Ho Lee, Sang In Shim; Korean J Pathol. 1998;32(3):208-214.

1,952 View
17 Download

Abstract PDF: We evaluated 1,000 consecutive endometrial curettage samples obtained over a 30 month period. The clinico-pathologic correlation was analysed according to Hendrickson's five criteria based on the practical view. The causes of uterine bleeding in decreasing order of occurrence were as follows: 1) hormonal imbalance lesions (49.2%) encompassing glandular and stromal breakdown suggesting anovulatory bleeding, proliferative phase endometrium, and disordered proliferative endometrium, 2) pregnancy associated lesions (24.2%), 3) organic lesions (13.5%), 4) endometrial hyperplasia (6.9%), and 5) inadequate specimen (6.2%). According to age, pregnancy related lesions were most frequent in the third decade. In the fourth, fifth, and sixth decades, hormonal imbalance lesions were the most common cause. In approximately 30% of the samples, there were two or three morphologic patterns such as anovulatory bleeding with an endometrial polyp, postabortal bleeding with inflammation, and glandular-stromal dissociation with a polyp, which suggested there was a variable histologic morphology in the same disease spectrum. Using immunohistochemical techniques we studied the hormonal dependency of bcl-2 oncoprotein in anovulatory bleeding, endometrial hyperplasia, and proliferative endometrium. 70% of anovulatory bleeding specimens showed weak positivity in the epithelial cytoplasm, and all cases of endometrial hyperplasia and carcinoma showed a strong positivity. These results suggest that there is a estrogenic hormonal dependency of apoptosis in the endometrium.

Expression of bcl-2 Protein in Gastric Adenoma and Adenocarcinoma.: Young Sill Kim, Byung Kee Kim, Sang In Shim; Korean J Pathol. 1998;32(4):248-254.

2,164 View
15 Download

Abstract PDF: The bcl-2 oncoprotein confers a survival advantage to cells by blocking programmed cell death. Overexpression of bcl-2 probably plays a role in tumorigenesis, and the expression of the bcl-2 protein has been investigated in many kinds of tumors. However, there have been only a few reports on expression of bcl-2 in human gastric adenocarcinoma. The aim of this study was to investigate the relationship between the expression of bcl-2 protein and several clinical and pathological parameters such as age, tumor site, size, histological type, depth of invasion, Lauren's classification, and grade. Immunohistochemical staining using monoclonal bcl-2 protein antibody, clone 124, was performed on paraffin embedded specimens from 23 gastric adenomas and from 45 gastric adenocarcinomas. The results are as follows. 1. Variable intensity of epithelial staining was noted from case to case, although the lymphocytic component showed similar intensity in all examples. The staining was located at the gland and mucous neck region of non-neoplastic epithelium. 2. The more differentiated type of gastric adenocarcinoma showed the higher expression rate and intensity. 3. The relationship between the expression rates of bcl-2 protein and tumor grade (adenoma early gastric adenocarcinoma advanced gastric adenocarcinoma) was statistically significant. The reactivity in adenoma was somewhat stronger with a uniform pattern, while in adenocarcinoma it was much weaker with a heterogenous pattern. 4. Intestinal type carcinomas by Lauren's criteria showed a higher expression rate and intensity than diffuse type. These results suggest that the bcl-2 expression would be found in the early phase of gastric tumorigenesis, and the expression rate and intensity would decrease according to the tumor progression.

Expression of p53, bcl-2 Proteins and Estrogen Receptors in Human Breast Cancer.: Hee Kyung Chang, Choong Han Lee, Man Ha Huh; Korean J Pathol. 1996;30(8):662-670.

2,109 View
24 Download

Abstract PDF: In 56 breast cancer tissues (infiltrating ductal carcinoma) with a clinical follow-up period of more than 5 years, positivity of estrogen receptor(ER) by enzyme immunoassay and expressions of bcl-2 and p53 oncoproteins by immunohistochemistry were evaluated. The purposes of this study were to determine prevalence of bcl-2 and p53 in breast cancer, the interrelationship between expression of the proteins and estrogen receptor, correlation between histologic grade and the expression of the tumor-related oncogenes, and to explore the biologic bahavior of breast cancer (lymph node metastasis, recurrence rate, and survival) via expression of bcl-2 and p53. Twelve of 56 (21.4%) carcinomas were bcl-2 positive, and seventeen (30.4%) were p53- positive. Eleven of 12 bcl-2 positive tumors (91.7%) were ER-positive, and bcl-2 expression was significantly associated with ER-positivity(P=0.043). Seven of 36 ER-positive tumors (12.5%) were p53 positive, and p53 expression was inversely associated with ER-positivity(P=0.006) significantly. The bcl-2 protein expression showed a significant relationship to low histologic grade of tumor (P=0.0002), and an almost significant relationship to lower recurrence rate (P=0.09). The p53 protein expression showed a significant relationship to high histologic grade of tumor (P=0.002) and an almost significant relationship to lymph node metastasis (P=0.09). Also an almost inverse relationship between bcl-2 and p53 was demonstrated (P=0.057). The bcl-2 expression had a tendency to be associated with longer patient survival(P= 0.09), but p53 immunoreaction was found not to be associated with shorter patient survival(P=0.16). These results provide further evidence that higher incidence of bcl-2 expression is correlated with higher incidence of ER and lower grade of tumor, while p53 expression is correlated with lower incidence of ER and higher grade of tumor. In conclusion, although the biologic function of bcl-2 protein is not yet well understood in breast cancer, our results suggest that bcl-2 and p53 oncoproteins might play significant roles in estrogen receptor and development of breast cancer. But their prognostic significance could not be determined; our results are 'not significant' but 'almost significant'. Thus, contribution of bcl-2 and p53 immunohistochemical phenotyping of breast cancer with ER to the clinical management need verification in larger series.

Expression of bcl-2 and p53 Protein in Premalignant Lesion and Invasive Squamous Cell Carcinoma of the Uterine Cervix.: Hyun Chang Joo, Kwan Kyu Park, Sang Sook Lee, Eun Sook Chang, Tae Sung Lee, Soon Do Cha, Young Jae Lee; Korean J Pathol. 2000;34(4):280-287.

2,378 View
32 Download

Abstract PDF: In order to understand the possible involvement of bcl-2 and p53 proteins in the tumorigenesis of the cervical cancer and precancerous lesion, we studied the expression patterns of bcl-2 and p53 proteins in 25 cases of carcinoma in situ, 12 cases of microinvasive cervical carcinoma, and 37 cases of invasive cervical carcinoma, respectively. By immunohistochemistry, 76% of in situ carcinoma, 83.3% of microinvasive cervical carcinoma, and 60.9% of invasive cervical carcinoma were positive for bcl-2, while the staining of basal cell layers, columnar cells, and squamous metaplastic epithelium of normal cervical epithelium were positive for bcl-2 in 91.9%, 73.1%, and 81.8% of cases, respectively. Furthermore, two out of fourteen cases of invasive cervical carcinoma with lymph node metastasis were positive for bcl-2. p53 was expressed in 72.7% of condyloma or dysplasia, 12% of in situ carcinomas, 33.3% of microinvasive cervical carcinoma, and 43.5% of invasive cervical carcinomas without metastasis. Six out of fourteen cases of invasive cervical carcinoma with lymph node metastasis were positive for p53 immunostaining. In contrast, 5.4% of basal cells and 9.1% of squamous epithelium, and none of the columnar cells in normal cervical epithelium were positive for p53. In summary, the bcl-2 protein was highly expressed in the proliferative lesion of reserve cells, such as normal reserve cells, columnar cells, squamous metaplasia, carcinoma in situ, and microinvasive squamous cell carcinoma. p53 expression was increased in condyloma, carcinoma in situ, and invasive carcinoma where the reserve cells were non-proliferative. Based on these findings, we propose that bcl-2 and p53 protein are involved in the development and progression of uterine cervical carcinoma.

Expression of Androgen Receptor, bcl-2 Protein and Rb Protein in Breast Cancers as Related to Prognostic Factors.: Hyun Deuk Cho, Young Sik Kim, Insun Kim; Korean J Pathol. 1998;32(6):443-452.

2,004 View
10 Download

Abstract: Breast cancer is the most common malignancy of women in industrialized countries and the third in Korean women. There have been a lot of studies on biologic behaviors as well as on the prognostic factors of the breast cancer. In this study, the expression of hormone receptors (estrogen receptor ; ER, progesterone receptor ; PR, and androgen receptor ; AR), bcl-2 and Rb proteins were immunostained on 60 infiltrating ductal carcinomas of the breast. The results were evaluated in relation with the age, histologic grade, tumor size, and status of lymph node metastasis. The expression of ER and PR had a significant inverse correlation with the histologic grade (p<0.001). The expression of AR was significantly correlated with the expression of ER (p=0.039) and PR (p=0.009), but not with other factors such as age, histologic grade, tumor size, and status of lymph node metastasis. There was no relationship between bcl-2 protein expresssion and other prognostic factors, except with the expression of ER. Rb protein expression had a significant positive relationship with PR (p=0.05) and the degree of positivity was correlated with histologic grade (p=0.002). In conclusion, this result suggests that expression of AR is well correlated with ER and PR. bcl-2 has no prognostic value. The significance of Rb protein expression remained to be studied.

Expression of bcl-2 and c-myc Proteins in Epidermal and Melanocytic Tumors.: Young Ha Oh, Chan Kum Park, Jung Dal Lee; Korean J Pathol. 1996;30(9):810-818.

2,124 View
25 Download

Abstract PDF: bcl-2 and c-myc protein expression were studied in 44 epidermal (8 seborrheic keratoses, 21 squamous cell carcinomas, and 15 basal cell carcinomas), and 26 melanocytic tumors(8 nevi, and malignant melanomas) by immunohistochemistry using the specific anti-bcl-2 and anti-c-myc monoclonal antibodies. 14 out of 15 basal cell carcinomas(BCC) (93.3%) showed expression of bcl-2 protein, 12 of which (85.7%) showed coexpression of c-myc protein. In the melanocytic tumors, 7 out of 8 nevi showed bcl-2 expression (87.5%). Five of these 7 cases (62.5%) also showed c-myc protein expression. Eight of 18 malignant melanomas(MM) (44.4%) showed expression of bcl-2 protein and 7 of these 8 cases (38.9%) also showed c-myc protein expression. All seborrheic keratoses and squamous cell carcinoma(SCC) were negative for bcl-2 proteins. 12 of 15 SCCs(80%) were positive for c-myc protein. In conclusion, bcl-2 and c-myc proteins were coexpressed in BCCs, nevi, and MMs. Coexpression of bcl-2 and c-myc proteins in these tumors was statistically significant(p<0.01), while no considerable differences of bcl-2 and c-myc expression were found between nevi and MMs. These results suggests that bcl-2 may cooperate with c-myc to promote tumorigenesis of BCCs, nevi, and MMs(p<0.01).

Classification of Gastrointestinal B-cell Lymphoma and Expression of Cyclin D1, bcl-2, bcl-6, p53 Protein and PCNA.: Ji Han Jung, An Hee Lee, Chang Suk Kang, Byung Kee Kim; Korean J Pathol. 2000;34(6):437-445.

2,081 View
16 Download

Abstract PDF: Until recently, the gastrointestinal lymphomas were classified according to the criteria developed for the node-based lymphomas. In recent years, the REAL classification provided a new category of MALT lymphoma and Mantle cell lymphoma in B-cell lymphomas. Low-grade MALT lymphomas have been well characterized clinically, histologically, and immunophenotypically. We retrospectively recategorized 41 cases of the primary gastrointestinal B-cell lymphoma and investigated the expression of cyclin D1, bcl-2, bcl-6, p53 protein, and PCNA by immunohistochemical method. The cases were categorized in 5 groups, low grade MALToma, low/high grade MALToma, high grade MALToma, diffuse large cell lymphoma, and mantle cell lymphoma according to the morphological findings. The expression of cyclin D1 protein was restricted to the cases of mantle cell lymphoma. The bcl-2 protein expression was higher in the low grade MALT lymphoma than in the high grade lymphoma (P=0.006). The bcl-2 protein expression was higher in the low grade area than in the high grade area in the low/high grade MALT lymphoma (P=0.005). The bcl-6 and p53 protein expression was higher in the high grade MALT lymphoma than in the low grade lymphoma (P=0.022, P<0.018). However, the bcl-6 protein expression of the tumor cells was higher in high grade area than in low grade area in the low/high grade MALT lymphoma (P=0.004). The degree of the PCNA expression was positively correlated with the grade of the malignant lymphoma (P=0.003). The above results suggest that the cellular proliferation assessed by PCNA index correlates with the histologic grade. And the bcl-2, bcl-6, p53 protein may be effective in the transition from the low grade MALT lymphoma to the high grade lymphoma. Therefore, we can differentiate the low grade lymphoma from the high grade lymphoma by the immunohistochemical staining for cyclin D1, bcl-2, bcl-6, p53 protein and can predict the prognosis of the patients in accordance with the grade of the tumor.

Prognostic Implications of Ki-67 Labelling Index and p53, bcl-2 Protein Expression in the Primary Central Nervous System Lymphoma.: Jae Ho Han, Woo Ick Yang, Tai Seung Kim; Korean J Pathol. 2000;34(6):456-464.

2,125 View
12 Download

Abstract PDF: It has been claimed that CNS lymphoma, a rare neoplasm accounting for only a small fraction of malignant brain tumors, occurs with increasing frequency in immunologically normal as well as immunocompromised individuals. We investigated the prognostic value of Ki-67 index, p53, and bcl-2 oncoprotein expression in relation to the clinicopathological parameters in the primary CNS lymphoma patients. The tumors were graded by Kiel classification and the Working formulation and included 33 high-grade, 4 intermediate-grade, and 5 low-grade lymphomas. The phenotype was determined in 38 cases: 30 were B cell type and 8 were T cell type. All cases displayed variable degrees of nuclear Ki-67 staining from 1.0% to 92.0% (mean 51.1%). A highly significant correlation was established between the proportion of Ki-67 positive cells and the classification into grades (p=0.0002) and phenotypes (p=0.0002). Overexpression of p53 and bcl-2 protein was found in 37.1% and 51.4% of 35 patients, respectively. And p53 expression was significantly increased in B cell type (p=0.02). On Kaplan-Meier survival curve, the phenotype, grade of tumors, and p53 and bcl-2 protein expression were not correlated with overall survival. On multivariate analyses, overall survival was independently influenced by Ki-67 index. In conclusion, it is suggested that Ki-67 proliferating index is the most important marker for predicting biologic behavior of the primary CNS lymphoma.

Expression of Survivin, HSP90, Bcl-2 and Bax Proteins in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis.: Sang Dae Lee, Sung Woong Park, Soon Auck Hong, Gui Young Kwon, Tae Jin Lee; Korean J Pathol. 2006;40(5):333-338.

2,189 View
23 Download

Abstract PDF: BACKGROUND
Survivin belongs to the inhibitor of apoptosis family, and it has recently been found to be expressed in most solid tumors. Therefore, its expression is suggested to have prognostic significance. However, no data are available concerning the significance of survivin for the carcinogenesis of bladder cancer.
METHODS
In order to induce urothelial tumor in the rat urinary bladder, 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was administered to male Sprague-Dawley rats for 30 weeks. We used immunohistochemistry to investigate the expressions of survivin, HSP90, Bcl-2 and Bax in rat bladder carcinogenesis.
RESULTS
Urothelial cell hyperplasia, papilloma, non-invasive urothelial carcinoma and invasive urothelial carcinoma appeared at 5, 10, 20 and 30 weeks, respectively. The expressions of survivin and HSP90 increased sequentially from normal mucosa, hyperplasia, papilloma, non-invasive urothelial carcinoma to invasive urothelial carcinoma. The expressions of Bcl-2 and Bax did not increase, however the number of cases with more than 1 of Bcl-2/Bax expression ratio increased sequentially during the progression of urothelial lesion. The expression of survivin showed a statistically significant correlation with the expression of HSP90 and the Bcl-2/Bax expression ratio.
CONCLUSIONS
Our findings suggest that survivin may be involved in the carcinogenesis of rat bladder and its expression is correlated with the expression of HSP90 and the Bcl-2/Bax expression ratio.

Correlation between Expression of p53 and Bcl-2 Protein and Epstein-Barr Virus Detection in Gastric Adenocarcinoma.: Ki Jung Yun, Weon Cheol Han, Hyung Bae Moon, Sang Woo Juhng; Korean J Pathol. 1998;32(8):574-580.

1,828 View
10 Download

Abstract: Epstein-Barr virus (EBV) has been known to be associated with a wide variety of neoplastic conditions including nasopharyngeal carcinoma, Hodgkin's disease, and non-Hodgkin's lymphoma. Recent studies reveal the presence of EBV in certain subtypes of gastric carcinoma in which EBV appears to be pathogenetically related. To evaluate the relationship between EBV and gastric adenocarcinoma, we examined EBV DNA using direct in situ polymerase chain reaction, and expression of p53 protein and bcl-2 protein using immunohistochemical staining method on paraffin embedded tissues. The materials consisted of one hundred twenty-eight gastric adenocarcinomas and twenty benign peptic ulcers. EBV DNA was detected in 14 of 128 gastric adenocarcinomas (10.9%). p53 protein was positive in 10 of 14 EBV positive adenocarcinomas (71.4%) and in 61 of 114 EBV negative adenocarcinomas (53.5%). Bcl-2 protein was positive in 2 of 14 EBV positive adenocarcinomas (14.3%) and in 19 of 114 EBV negative adenocarcinomas (16.7%). The above results indicate that EBV is associated with gastric adenocarcinoma, and p53 protein may play a role in carcinogenesis of EBV in gastric adenocarcinoma.

A Comparative Study of Immunohistochemical Expression of p53, bcl-2, c-erbB-2, and MIB-1 in Polypoid and Infiltrative Colorectal Carcinomas.: Jeong Seok Moon, Seong Hwan Park, Bong Kyong Shin, Ju Han Lee, Joon Ho Shin, Bom Woo Yeom; Korean J Pathol. 1998;32(8):581-589.

1,920 View
10 Download

Abstract: Almost all colorectal carcinomas have been thought to develop from pre-existing adenomas. However, some colorectal carcinomas can arise directly from normal flat mucosa, and usually form infiltrative mass at the early stage. The carcinogenesis of this infiltrative carcinoma may be different from the well-known adenoma-carcinoma sequence, which usually forms a polypoid mass. The purpose of this study is to investigate the different expression of various oncogenes in polypoid carcinoma and infiltrative carcinoma. We performed immunohistochemical staining on p53, bcl-2, c-erbB-2 and MIB-1 in 29 polypoid carcinomas arised from adenomas, and 21 infiltrative carcinomas. The average tumor size of infiltrative carcinomas (5.5 cm) was larger than that of polypoid carcinomas (3.1 cm), and the polypoid carcinomas were differentiated more than the infiltrative carcinomas. The results of p53, bcl-2, c-erbB-2, and MIB-1 antisera immunoreactivity in the polypoid carcinoma were 79%, 17%, 21%, and 100%, and those in the infiltrative carcinoma were 71%, 29%, 29%, and 100%, respectively. However the diffuse positivities of p53 and MIB-1 antisera were slightly higher in the infiltraive carcinomas (62%, 76%) than in the polypoid carcinomas (55%, 41%) (p=0.63, 0.01). And the results of p53 and c-erbB-2 immunoreactivity in the adenomas were 52% and 17%, respectively, which is significantly lower than that in the polypoid carcinoma(p=0.03, 0.74). The immunoreactivty of bcl-2 in the adenoma was 72%, which was significantly higher than that in the polypoid carcinoma (17%) (p<0.01). In summary, we did not show the significant difference in expression of p53, bcl-2, c-erbB-2, and MIB-1 proteins between polypoid and infiltrative carcinomas. However, the tendency of infiltrative carcinomas having a more aggressive nature suggests another carcinogenetic mechanism is involved in the colorectal carcinogenesis.

Clinicopathological Analysis of Systemic Anaplastic Large Cell Lymphoma.: Soo Young Chung, Han Suk Ryu, Jae Soo Ko, Baek Youl Ryoo, Seung Sook Lee; Korean J Pathol. 2006;40(6):399-405.

2,146 View
19 Download

Abstract PDF: BACKGROUND
Several studies from western countries have reported variable prognoses for patients with systemic anaplastic large cell lymphoma (ALCL) depending strongly on the expression of anaplastic lymphoma kinase (ALK). However, no prognostic significance of ALK expression in Koreans was reported in a single report regarding these patients, although the number of cases was limited in that study.
METHODS
We analyzed the clinicopathological features of ALK+ ALCL and ALK- ALCL in 30 Korean patients diagnosed with primary systemic ALCL.
RESULTS
ALK expression was detected in 60% of all ALCL patients (18/30), and there was no statistical significance to ALK expression in overall survival. Patients with ALK+ ALCL were younger in age and had negative bcl-2 expression; these differences were statistically significant. Tumors positive for ALK protein and granzyme B expression, and negative for bcl-2 expression with a null-cell phenotype tended to have better survival outcomes, althought this trend failed to reach statistical significance (p<0.2), probably due to the limited number of cases in this study.
CONCLUSION
ALK protein expression and the absence of bcl-2 in tumor cells tend to result in better survival despite the failure of this trend to achieve statistical significance. Further studies that examine potential pathologic prognostic factors combined with the expression of ALK and apoptotic factors such as bcl-2 are needed. Additional larger-scale studies are also needed to conclude that ALK expression has no prognostic significance among Koreans.

Expression of bcl-2 and p53 Protein, and Apoptosis in Transitional Cell Carcinoma of the Bladder.: Myoung Ja Chung, Sang Su Kim, Ho Yeul Choi; Korean J Pathol. 2000;34(8):567-573.

1,960 View
12 Download

Abstract PDF: This study examined the expression of the bcl-2 protein in 59 cases of transitional cell carcinomas (TCCs) of the bladder and evaluated the relationship of bcl-2 and p53 with apoptosis. The cases were divided into 41 low-grade TCCs, 18 high-grade TCCs, 32 superficial TCCs, and 27 invasive TCCs. p53 and bcl-2 protein were detected by the immunohistochemical method and apoptosis was analysed by using hematoxylin-eosin stained slide. The results were as follows: bcl-2 protein was detected in 8 (14%) TCCs and all of these cases were low grade TCCs. Expression of bcl-2 protein was not correlated with clinical stage. There was no correlation between bcl-2 and p53 protein. According to the immunohistochemical results of bcl-2 and p53 protein, the cases were divided 4 groups. Apoptotic index (AI) was higher in p53 positive/ bcl-2 negative group than other groups but the significance was recognized only between p53 positive/bcl-2 negative group and p53 negative/bcl-2 negative group (p<0.05). p53 protein was detected in 20 (36%) TCCs and its expression was correlated positively with histologic grade and clinical stage (p<0.05). AI correlated positively with histologic grade and clinical stage (p<0.01). These data indicate that overexpression of bcl-2 protein is rare in TCC of the bladder and associated with low grade TCCs. Overexpression of p53 is associated with the tumor progression in the TCCs. AI correlates with p53 positivity but does not correlate with bcl-2 positivity.

Expression of bcl-2 and p53 Protein in Primary Gastric Lymphomas.: Young Rok Cho, Yu Na Kang, Sang Sook Lee, Hong Suk Song, Soo Sang Sohn, Dong Sug Kim; Korean J Pathol. 1998;32(11):978-984.

2,513 View
10 Download

Abstract: The bcl-2 gene is a proto-oncogene which extends cell survival by blocking apoptosis. Bcl-2 expression has been detected in many types of nodal and MALT lymphoma. The p53 gene is a tumor suppressor gene and p53 mutation is the most common genetic alteration in human malignancies. The relationship between the expression of bcl-2 and p53 protein in primary gastric lymphoma has been rarely reported. The authors investigated the expression of bcl-2 and p53 protein in 37 cases of primary gastric lymphoma by immunohistochemical method using bcl-2 and p53 monoclonal antibodies. There were five cases of low grade B-cell MALT lymphomas and thirty two cases of high grade B-cell lymphomas. Fifteen of 37 cases (41%) showed bcl-2 protein expression in the cytoplasm of tumor cells and 26 cases (70%) showed p53 protein expression in the nucleus of tumor cells. Bcl-2 protein was detected in 4 of 5 (80%) low grade MALT lymphomas, and in 11 of 32 (34%) high grade lymphomas. There was no significant correlation between bcl-2 expression and histologic grade of primary gastric lymphomas (p>0.05). p53 protein was positive in 25 of 32 (78%) high grade lymphomas, and in 1 of 5 (20%) low grade MALT lymphomas. The expression of p53 protein is significantly higher in high grade lymphoma than in low grade MALT lymphoma (p<0.05). The p53 expression in the bcl-2 negative cases (86%) was significantly higher than in the bcl-2 positive cases (47%). There was an inverse relationship between bcl-2 and p53 expression in primary gastric lymphoma. These results suggest that bcl-2 and p53 expression in primary gastric lymphoma may be involved in the transition from low grade MALT lymphoma to high grade lymphoma.

Prognostic Significance of the Tall Cell Variant of Papillary Thyroid Carcinoma: Expression of p53, bcl-2 & Leu-M1 proteins.: Won Mi Lee, Joo Seob Keum, Eun Kyung Hong, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1998;32(11):1000-1007.

1,999 View
10 Download

Abstract: Papillary carcinoma of the thyroid is a well differentiated neoplasm and usually has a good prognosis. However, a subset of morphologically distinct papillary carcinoma has bad prognoses. The tall cell variant of papillary carcinoma (TCPC), characterized by tall columnar cells with a height at least twice the width, is the one of these. In order to differentiate TCPC from usual papillary carcinoma (UPC) in terms of prognosis, we performed immunohistochemical studies for the expression of p53, bcl-2 and Leu-M1 proteins in 25 cases of TCPC, 26 cases of UPC and 14 cases of poorly differentiated, solid type papillary carcinoma (SPC) with an analysis of clinical parameters. The nuclear expression of p53 was noted in one case each of UPC and TCPC. The cytoplasmic p53 expression of TCPC, UPC, and SPC was observed in 17/25 cases (68%), 14/26 cases (54%), 3/14 cases (21%), respectively. bcl-2 expression was 19/25 cases (76%), 18/26 cases (69%), 5/14 cases (36%), and that of Leu-M1 was 21/25 cases (84%), 18/26 cases (69%), 4/14 cases(29%), respectively. There were no statistical significance in the expression of those immunoproteins among these three groups (p>0.05). The p53 protein was consistently expressed in the cytoplasm rather than nucleus in this study and was very well correlated to bcl-2 positivity (p<0.01). There were no statistical significance in any clinical parameters examined among these three groups (p>0.05). In conclusion, TCPC can not be separated from UPC as a distinct entity in this study and the cytoplasmic expression of p53 protein provides another mechanism of p53 inactivation in tumorigenesis of the thyroid papillary carcinoma, possibly by bcl-2 related mechanism.

Correlation between bcl-2 and Caspase-3 Expression and Proliferating Activity in Squamous Neoplasia of the Uterine Cervix.: Kyung Sun Park, Mi Seon Kang, Hye Kyoung Yoon; Korean J Pathol. 2000;34(11):919-926.

1,864 View
12 Download

Abstract PDF: Detailed mechanism of uterine cervical cancer progression still remains unclear. Altered programmed cell death (apoptosis) and cellular proliferation are associated with the development of neoplasia. The authors investigated the expressions of bcl-2, which inhibit apoptosis, and caspase-3, which is involved in the induction of apoptosis and has been considered to be correlated with apoptosis, and proliferating activity according to the degree of malignancy in the squamous neoplasia of the uterine cervix. Correlation between bcl-2 and caspase-3 expression and proliferating activity was done. The materials were low grade squamous intraepithelial lesions (LSIL, n=15), high-grade squamous intraepithelial lesions (HSIL, n=15), microinvasive squamous cell carcinoma (n=15), and squamous cell carcinoma (n=15). Immunohistochemical stainings for bcl-2, caspase-3, and MIB-1 were done. bcl-2 and MIB-1 expressions were progressively increased in accordance with the increasing degree of malignancy, but caspase-3 immunoreactivity was higher in LSIL than invasive cancers. There was an inverse relationship between bcl-2 and caspase-3 expression, but the difference did not reach statistical significance. No significant correlation between MIB-1, bcl-2, and caspase-3 expressions was observed. These results suggest that an inhibition of apoptosis and the augmentation of proliferating activity of tumor cells might be separately involved in the development of the cervical squamous neoplasia.

Expression of p21, p53 and bcl-2 Proteins in Invasive Ductal Carcinoma of the Breast.: Hyang Jeong Jo, Ki Jung Yun, Hyung Bae Moon; Korean J Pathol. 2003;37(6):393-399.

2,021 View
24 Download

Abstract PDF: BACKGROUND
This study was designed to investigate the prognostic significance of p21, p53, and bcl-2 proteins in invasive ductal carcinoma of the breast.
METHODS
Seventy-two cases of invasive ductal carcinoma were examined by immunohistochemical staining for p21, p53 and bcl-2 proteins. The results were correlated with clinicopathological variables, including age, tumor size, histologic grade, nuclear grade, lymph node status, estrogen receptor (ER) and progesterone receptor (PR) expression.
RESULTS
Of 72 cases, p21, p53 and bcl-2 proteins were positive in 25 (34.8%), 35 (50.0%) and 27 (37.5%), respectively. There were no statistically significant correlations between the p21 protein expression and the other clinicopathological variables. The expression of p53 protein, however, showed a significant relation to ER expression, and that of bcl-2 was positively correlated with tumor size. In survival analysis, p21, p53, and bcl-2 proteins, nuclear grade and lymph node status were associated with survival rate.
CONCLUSIONS
These results indicate that p21, p53, and bcl-2 proteins might play a role in tumorigenesis of breast carcinoma. In addition, the increased expression of p21, p53, and bcl-2 proteins could be used as factors suggesting poor prognosis in breast carcinomas.

Telomerase Activity and Expression of MIB-1 and bcl-2 in Human Chorionic Villi from Early and Term Normal Pregnancy.: Jung Sook Cho, Young Soon Kang, In Gul Moon, Bum Chae Choi, Jong Pyo Lee, Hoon Taek Lee, Sung Ran Hong; Korean J Pathol. 2000;34(11):927-933.

2,247 View
12 Download

Abstract PDF: Telomerase is an enzyme that maintains telomeres and prevents telomere shortening, and may be linked with cellular proliferation or the aging process. The purpose was to examine telomerase activity in human chorionic villi from early and term normal pregnancies, and to analyze the correlation of telomerase activity (TA) with MIB-1 & bcl-2. A total of 37 placentae were obtained from 16 early and 21 term pregnancies. TA was assayed by telomeric repeat amplification protocol, and immunohistochemical staining was performed for MIB-1 & bcl-2 expression. TA & MIB-1 expression were strong in early placenta, but bcl-2 was highly expressed in term placentae. Thirteen (81.25%) of 16 early placentae showed TA, but only 2 (9.52%) of 21 term placentae expressed TA (p<0.01). MIB-1 was observed in nuclei of cytotrophoblast, and the expression rate was 16.09% in early placentae and 2.87% in term placentae (p<0.01). bcl-2 was observed only in the cytoplasm of syncytiotrophoblast. Term placenta demonstrated stronger expression of bcl-2 compared to early placentae (p<0.05). These findings suggest that TA, MIB-1 & bcl-2 expression are critically regulated over the course of gestation: cytotrophoblast, main cells of early chorionic villi, may be a common source of telomerase and proliferative activity. The TA showed good correlation with cellular proliferative activity. Syncytiotrophoblast, may be a main source of bcl-2 expression which is stronger in the term placentae.

First
Prev
Page of 2
Next
Last

Search