Journal of Pathology and Translational Medicine

Original Articles

The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence: Jee Soon Kim, Youn Soo Lee, Min Jung Jung, Yong Kil Hong; J Pathol Transl Med. 2016;50(6):419-425. Published online October 6, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.30

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Background
The 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence.
Methods
One hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence.
Results
Analysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01).
Conclusions
Based on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

Citations

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The Value of ER∝ in the Prognosis of GH- and PRL-Secreting PitNETs: Clinicopathological Correlations
Roxana-Ioana Dumitriu-Stan, Iulia-Florentina Burcea, Valeria Nicoleta Nastase, Raluca Amalia Ceaușu, Anda Dumitrascu, Laurentiu Catalin Cocosila, Alexandra Bastian, Sabina Zurac, Marius Raica, Catalina Poiana
International Journal of Molecular Sciences.2023; 24(22): 16162. CrossRef
Ki-67/MIB-1 and Recurrence in Pituitary Adenoma
Kent Tadokoro, Colten Wolf, Joseph Toth, Cara Joyce, Meharvan Singh, Anand Germanwala, Chirag Patel
Journal of Neurological Surgery Part B: Skull Base.2022; 83(S 02): e580. CrossRef
Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas
Su Jung Kum, Hye Won Lee, Soon Gu Kim, Hyungsik Park, Ilseon Hwang, Sang Pyo Kim
Journal of Pathology and Translational Medicine.2022; 56(1): 22. CrossRef
A Preoperative MRI-Based Radiomics-Clinicopathological Classifier to Predict the Recurrence of Pituitary Macroadenoma Within 5 Years
Yu Zhang, Yuqi Luo, Xin Kong, Tao Wan, Yunling Long, Jun Ma
Frontiers in Neurology.2022;[Epub] CrossRef
Endoscopic Endonasal Pituitary Surgery For Nonfunctioning Pituitary Adenomas: Long-Term Outcomes and Management of Recurrent Tumors
Anne-Laure Bernat, Pénélope Troude, Stefano Maria Priola, Ahmad Elsawy, Faisal Farrash, Ozgur Mete, Shereen Ezzat, Sylvia L. Asa, John De Almeida, Allan Vescan, Eric Monteiro, Joao Paulo Almeida, Gelareh Mohammed Zadeh, Fred Gentili
World Neurosurgery.2021; 146: e341. CrossRef
A Nomogram for Preoperatively Predicting the Ki-67 Index of a Pituitary Tumor: A Retrospective Cohort Study
Xiangming Cai, Junhao Zhu, Jin Yang, Chao Tang, Feng Yuan, Zixiang Cong, Chiyuan Ma
Frontiers in Oncology.2021;[Epub] CrossRef
Comparative Proteomic Study Shows the Expression of Hint-1 in Pituitary Adenomas
Carolina Carrillo-Najar, Daniel Rembao-Bojórquez, Martha L. Tena-Suck, Sergio Zavala-Vega, Noemí Gelista-Herrera, Miguel A. Ramos-Peek, Juan L. Gómez-Amador, Febe Cazares-Raga, Fidel de la Cruz Hernández-Hernández, Alma Ortiz-Plata
Diagnostics.2021; 11(2): 330. CrossRef
Prediction of recurrence in solid nonfunctioning pituitary macroadenomas: additional benefits of diffusion-weighted MR imaging
Ching-Chung Ko, Tai-Yuan Chen, Sher-Wei Lim, Yu-Ting Kuo, Te-Chang Wu, Jeon-Hor Chen
Journal of Neurosurgery.2020; 132(2): 351. CrossRef
Pituitary tumors: epidemiology and clinical presentation spectrum
Marta Araujo-Castro, Víctor Rodríguez Berrocal, Eider Pascual-Corrales
Hormones.2020; 19(2): 145. CrossRef
Ki67 in endocrine neoplasms: to count or not to count, this is the question! A systematic review from the English language literature
E. Guadagno, E. D’Avella, P. Cappabianca, A. Colao, M. Del Basso De Caro
Journal of Endocrinological Investigation.2020; 43(10): 1429. CrossRef
Study of Simple Immunohistochemical Cytocolorimetric Assay Application for More Accurate Assessment of Prognosis in Patients with Pituitary Adenomas
Pavel V. Nikitin, Marina V. Ryzhova, Lyudmila V. Shishkina, Svetlana V. Shugay, Irina V. Zubova
World Neurosurgery.2019; 122: e1047. CrossRef
The Prognostic Roles of the Ki-67 Proliferation Index, P53 Expression, Mitotic Index, and Radiological Tumor Invasion in Pituitary Adenomas
Rovshan Hasanov, Berna İmge Aydoğan, Saba Kiremitçi, Esra Erden, Sevim Güllü
Endocrine Pathology.2019; 30(1): 49. CrossRef
Residual Tumor Confers a 10-Fold Increased Risk of Regrowth in Clinically Nonfunctioning Pituitary Tumors
Jelena Maletkovic, Asmaa Dabbagh, Dongyun Zhang, Abdul Zahid, Marvin Bergsneider, Marilene B Wang, Michael Linetsky, Noriko Salamon, William H Yong, Harry V Vinters, Anthony P Heaney
Journal of the Endocrine Society.2019; 3(10): 1931. CrossRef
Atypical pituitary adenoma: a clinicopathologic case series
Martin J. Rutkowski, Ryan M. Alward, Rebecca Chen, Jeffrey Wagner, Arman Jahangiri, Derek G. Southwell, Sandeep Kunwar, Lewis Blevins, Han Lee, Manish K. Aghi
Journal of Neurosurgery.2018; 128(4): 1058. CrossRef
Both invasiveness and proliferation criteria predict recurrence of non-functioning pituitary macroadenomas after surgery: a retrospective analysis of a monocentric cohort of 120 patients
Julie Lelotte, Anne Mourin, Edward Fomekong, Alex Michotte, Christian Raftopoulos, Dominique Maiter
European Journal of Endocrinology.2018; 178(3): 237. CrossRef
Letter to the Editor. Atypical pituitary adenoma
Lauren E. Rotman, T. Brooks Vaughan, James R. Hackney, Kristen O. Riley
Journal of Neurosurgery.2018; 129(6): 1657. CrossRef
Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies
Anna Angelousi, Georgios K Dimitriadis, Georgios Zografos, Svenja Nölting, Gregory Kaltsas, Ashley Grossman
Endocrine-Related Cancer.2017; 24(6): R239. CrossRef

Prognostic Significance of Heat Shock Protein 70 Expression in Early Gastric Carcinoma: Youngran Kang, Woon Yong Jung, Hyunjoo Lee, Wonkyung Jung, Eunjung Lee, Bong Kyung Shin, Aeree Kim, Han Kyeom Kim, Baek-hui Kim; Korean J Pathol. 2013;47(3):219-226. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.219

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Abstract PDF

Background

Overexpression of heat shock protein 70 (HSP70) has been observed in many types of cancer including gastric adenocarcinomas, although the exact role of HSP70 in carcinogenesis remains unclear.

Methods

The study analyzed a total of 458 radical gastrectomy specimens which were immunohistochemically stained with HSP70, p53, and Ki-67 antibodies.

Results

The study determined that the expression of HSP70 was significantly increased in early gastric cancer (EGC) compared to advanced gastric cancer (p<0.001). The HSP70 expression was correlated with well-differentiated tumor type, intestinal type of Lauren classification and the lower pT and pN stage. Negative expression of Ki-67 and p53 expression was associated with poor prognosis. The study did not find any correlation between HSP70 and p53 expression. The study determined that HSP70 expression in the EGC subgroup was associated with a poor prognosis (p=0.009), as well as negative Ki-67 expression (p=0.006), but was not associated with p53. Based on multivariate analysis, HSP70 expression (p=0.024), negative expression of Ki-67, invasion depth and lymph node metastasis were determined to be independent prognostic markers.

Conclusions

HSP70 is expressed in the early stages of gastric adenocarcinoma. In EGC, HSP70 is a poor independent prognostic marker and is correlated with a low proliferation index.

Citations

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The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach
Mahdieh Razmi, Fatemeh Tajik, Farideh Hashemi, Ayna Yazdanpanah, Fatemeh Hashemi-Niasari, Adeleh Divsalar
Journal of Gastrointestinal Cancer.2024;[Epub] CrossRef
Clinicopathological significance of HSP70 expression in gastric cancer: a systematic review and meta-analysis
Xiaolu Wang, Li Xie, Lijing Zhu
BMC Gastroenterology.2021;[Epub] CrossRef
Beta-sheet-specific interactions with heat shock proteins define a mechanism of delayed tumor cell death in response to HAMLET
Aftab Nadeem, James C.S. Ho, Tuan Hiep Tran, Sanchari Paul, Victoria Granqvist, Nadege Despretz, Catharina Svanborg
Journal of Molecular Biology.2019; 431(14): 2612. CrossRef
Evolving paradigms on the interplay of mitochondrial Hsp70 chaperone system in cell survival and senescence
Shubhi Srivastava, Vinaya Vishwanathan, Abhijit Birje, Devanjan Sinha, Patrick D’Silva
Critical Reviews in Biochemistry and Molecular Biology.2019; 54(6): 517. CrossRef
Clinicopathologic significance and prognostic value of Ki-67 expression in patients with gastric cancer: a meta-analysis
Guanying Luo, Yunzhao Hu, Zhiqiao Zhang, Peng Wang, Zhaowen Luo, Jinxin Lin, Canchang Cheng, You Yang
Oncotarget.2017; 8(30): 50273. CrossRef
Extracellular HSP70-peptide complexes promote the proliferation of hepatocellular carcinoma cells via TLR2/4/JNK1/2MAPK pathway
Yi Zhe, Yan Li, Dan Liu, Dong-Ming Su, Jin-Gang Liu, Hang-Yu Li
Tumor Biology.2016; 37(10): 13951. CrossRef
The cytomegalovirus protein UL138 induces apoptosis of gastric cancer cells by binding to heat shock protein 70
Wenjing Chen, Kezhi Lin, Liang Zhang, Gangqiang Guo, Xiangwei Sun, Jing Chen, Lulu Ye, Sisi Ye, Chenchen Mao, Jianfeng Xu, Lifang Zhang, Lubin Jiang, Xian Shen, Xiangyang Xue
Oncotarget.2016; 7(5): 5630. CrossRef
Targeting the hsp70 gene delays mammary tumor initiation and inhibits tumor cell metastasis
J Gong, D Weng, T Eguchi, A Murshid, M Y Sherman, B Song, S K Calderwood
Oncogene.2015; 34(43): 5460. CrossRef

Expression of DNA Topoisomerase II-alpha as a Proliferating Marker in Urothelial Carcinoma of Urinary Bladder based on World Health Organization/International Society of Urological Pathology Consensus Classification: A Correlation with Expression of Ki-67 and Apoptosis: Tae Jin Lee, Dong Ki Lee, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2002;36(5):305-313.

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Abstract PDF: BACKGROUND
DNA topoisomerase II-alpha is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relationship between the expression of DNA topoisomerase II-alpha as a proliferating marker, and the expression of Ki-67 and apoptosis in urothelial carcinoma of urinary bladder based on World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification.
METHODS
73 urothelial carcinomas of the urinary bladder after transurethral resection and 25 carcinomas after radical cystectomy were investigated for histologic grading based on WHO and WHO/ISUP consensus classification. Formalin fixed, paraffin embedded tissue of 98 specimens from 73 patients were immunohistochemically stained for DNA topoisomerase II-alpha and Ki-67, and in situ TdT-mediated dUTP-biotin nick end labeling method for evaluation of apoptotic cells was performed. For each case, a DNA topoisomerase II-alpha, Ki-67, and apoptotic indices were determined.
RESULTS
The histologic grades of 73 cases based on the WHO grading system were 21.9% (16 cases) in grade 1, 65.8% (48 cases) in grade 2, and 12.3% (9 cases). 5.5% (4 cases) of papillary neoplasm of low malignant potential, 47.9% (35 cases) of urothelial carcinoma of low grade, and 46.6% (34 cases) in urothelial carcinoma of high grade were reclassified using the WHO/ISUP consensus classification. Histologic grades based on two grading systems were correlated to invasion and stage (p<0.05). DNA topoisomerase II-alpha, Ki-67, and apoptotic indices were correlated to histologic grades based on two grading system and invasion. Also, the correlation of DNA topoisomerase II-alpha and Ki-67 indices, and DNA topoisomerase II-alpha and apoptotic indices were significant, respectively.
CONCLUSIONS
DNA topoisomerase II-alpha appears to be an useful marker for assessing the proliferation potential of urothelial carcinoma of in the urinary bladder.

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

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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

The Expressions of E2F1 and p53 in Gastrointestinal Stromal Tumors and Their Prognostic Significance.: Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Jong Seok Lee, Chan Heun Park, Woon Geon Shin; Korean J Pathol. 2009;43(3):212-220.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.212

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Abstract PDF

BACKGROUND
E2F1 plays a critical role in the G1-to-S phase transition by inducing various genes that encode S phase-activating proteins and that modulate such diverse cellular functions as DNA synthesis, mitosis and apoptosis. The purpose of this study was to assess the E2F1 expression in relation to the clinicopathologic parameters and other tumor markers in gastrointestinal stromal tumors.
METHODS
Immunohistochemical stainings for obtaining the E2F1, p53, and Ki-67 labeling indices were performed on a tissue microarray of 72 gastrointestinal stromal tumor specimens. The clinicopathologic parameters that were analyzed including the risk grade system by Miettinen et al. and the disease-free survival (DFS) rate.
RESULTS
1) An E2F1 expression was correlated with a larger tumor size, a p53 expression and a shorter period of DFS (p=0.014, p=0.007, and p=0.039). 2) A p53 expression was significantly associated with a high risk grade, a larger tumor size, high mitotic counts and a shorter period of DFS (p=0.003, p=0.044, p<0.001, and p<0.0001). 3) A high-risk grade and the epithelioid type were significantly associated with a shorter period of DFS (p=0.0006 and p=0.0008).
CONCLUSIONS
E2F1, as well as p53, may be a potentially novel independent prognostic factor for predicting a worse outcome for those patients suffering with Gastrointestinal stromal tumors.

Citations

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Comparison of tissue microarray and full section in immunohistochemistry of gastrointestinal stromal tumors
Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Jun Ho Park, Chan Heun Park, Won Jae Lee
Pathology International.2009; 59(12): 851. CrossRef

Caspase 3 and Ki-67 Immunoreactivity and Its Correlation with Frequency of Apoptosis in Gastric Adenomas and Carcinomas.: Jin Hee Sohn, Seoung Wan Chae, Kyung Chan Choi, Hyung Sik Shin; Korean J Pathol. 2001;35(4):286-290.

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Abstract PDF: BACKGROUND
Apoptosis, also known as programmed cell death, is under genetic control and is mediated by apoptosis-specific genes, certain oncogenes and tumor suppressor genes. Caspase 3, a group of cystein proteases, is involved in the induction of apoptosis and has been considered to be correlated with apoptosis. Therefore, we tried to define whether caspase 3 is expressed in gastric adenoma and carcinoma, and correlated with apoptosis.
METHODS
The apoptotic index and caspase 3 and Ki-67 immunoreactivity were observed in 25 gastric adenomas, 31 early gastric carcinomas (EGC) and 64 advanced gastric carcinomas (AGC) by in situ labelling and immunohistochemistry. RESULTS: The mean number of apoptotic bodies and caspase 3 immunoreactivity were significantly increased from adenoma through EGC to AGC. Ki-67 immunoreactivity was more increased in AGC than in adenoma and EGC. And the number of apoptotic bodies were positively correlated with caspase 3 and Ki-67 immunoreactivity, and caspase 3 immunoreactivity was negatively correlated with Ki-67 immunoreactivity even though they were statistically insignificant.
CONCLUSIONS
Our results suggest that caspase 3 activation is important for inducing apoptosis, and both caspase 3 and apoptosis are increased along the tumor progression.

Expressions and Diagnostic Usefulness of MIB-1 and p53 in Uterine Smooth Muscle Tumors.: Mi Jin Kim, Yong Jin Kim, Seung Ho LeeSeungHo; Korean J Pathol. 2001;35(6):524-530.

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Abstract: BACKGROUND
Controversy still remains concerning the criteria for the categorization of uterine smooth muscle tumors by conventional histologic examination. Various ancillary techniques have been used to improve diagnostic accuracy.
METHODS
Immunohistochemical study of MIB-1 and p53 was performed on 10 usual leiomyomas (UL), 13 cellular leiomyomas (CL), 5 bizarre leiomyomas (BL), 2 cases of intravenous leiomyomatosis (IL), 5 smooth muscle tumors of uncertain malignant potential (STUMP) and 8 leiomyosarcomas (LMS), to investigate the diagnostic value of MIB-1 and p53 in uterine smooth muscle tumors.
RESULTS
The MIB-1 labelling index was low in ULs and their variants (mean 5.67+/-5.53), but it was increased in STUMPs (17.67+/-6.51) and markedly increased in LMSs (35.71+/-11.35). In ULs and their variants, no immunostaining for p53 was noted except in one case of BL, while 2 (40%) of 5 STUMPs and 3 (38%) of 8 LMSs showed positive reactions for p53. There were significant differences among leiomyoma, STUMP and LMS in the MIB-1 labelling index and p53 expression.
CONCLUSIONS
These results suggest that both abnormal expressions of p53 and a high MIB-1 labelling index are frequently associated with leiomyosarcoma. Our data also indicate that the classification system of Kempson and Hendrickson is well correlated with the MIB-1 labelling index.

Ki-67 Labelling Index and Bax Expression According to the Capsular Invasion in the Follicular Neoplasms of the Thyroid.: Hee Kyung Kim, Dong Wha Lee, So Young Jin, Dong Won Kim; Korean J Pathol. 2001;35(6):531-535.

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Abstract: BACKGROUND
There have been a few studies concerning the differential diagnosis between follicular adenomas and minimally invasive follicular carcinomas, but it is difficult to exclude the possibility of minute capsular and/or vascular invasion throughout the capsular areas as a whole.
METHODS
We examined the diagnostic usefulness of Ki-67 labelling index and bax expression for the differential diagnosis of follicular adenomas and minimally invasive follicular carcinomas.
RESULTS
The result of immunohistochemical staining with Ki-67 and bax antibodies were analyzed in 58 cases of follicular neoplasms from 1996 to 1999. Of 58 cases, 35 were follicular adenomas and 23 were minimally invasive follicular carcinomas. The Ki-67 labelling index was significantly higher in minimally invasive follicular carcinoma of the thyroid (Ki-67 labelling index, 1.62+/-0.35%) than follicular adenoma (0.46+/-0.21%) (P<0.05). Of the follicular adenomas, Ki-67 labelling index of the tumor with 5 cm or more in diameter was 0.38+/-0.13%, while that of the tumor with less than 5 cm was 0.51+/-0.24%. Of the minimally invasive follicular carcinoma, Ki-67 labelling index of the tumor with 5 cm more was 1.30+/-0.07%, while that of the tumor with less than 5 cm was 1.65+/-0.37%. Diffuse bax expression was seen in 27 of 35 cases of follicular adenomas and 2 of 23 cases of minimally invasive follicular carcinoma (P<0.05).
CONCLUSIONS
Our findings suggest Ki-67 labelling index and the degree of bax expression are useful markers for the differential diagnosis between the follicular adenoma and the minimally invasive follicular carcinoma of the thyroid.

Differentiation, Proliferative Index, and Caspase 3 Expression Rate in the Immunohistochemical Stains of Medulloblastoma as Prognostic Factors.: Sung Eun Kim, Woo Ick Yang, Tai Seung Kim; Korean J Pathol. 2001;35(6):536-543.

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Abstract: BACKGROUND
Medulloblastoma is a highly malignant neuroepithelial tumor of the childhood, less frequently, of adults, located in the posterior cranial fossa. It shows multiple lines of differentiation, expressing neuronal, glial, mesenchymal and ectodermal markers. The prognostic significance of cell differentiation has been studied, but received little agreement. In highly malignant tumors, very high proliferative index has been demonstrated. A major contributor to cell loss in medulloblastoma is reported to be apoptosis. In medulloblstoma, a linear relation between apoptotic index and proliferative index has not been convincingly demonstrated.
METHODS
We analyzed the immunohistochemical features, proliferative indices and apoptotic indices in medulloblastoma patients with regard to their clinical courses. Clinical features of 58 patients with medulloblastoma were reviewed. The presence of glial fibrillary acidic protein, synaptophysin, vimentin, and epithelial membrane antigen were examined with immunohistochemical method. The proliferative index (Ki-67) and caspase 3 expressing rate were calculated.
RESULTS
There was no significant correlation between the prognosis and the degree of cell differentiation. The positive correlation was noted between proliferative index and apoptotic index in a tumor mass.
CONCLUSIONS
Only proliferative index could be used as a prognostic factor.

Ganglion Cell Tumors.: Sung Hye Park, Harry V Vinters; Korean J Pathol. 2002;36(3):167-174.

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Abstract PDF: BACKGROUND
In ganglion cell tumos, immunohistochemical characteristics and malignant changes of neuronal cells and the usefulness of the MIB-1 (Ki67) indices for granding ganglion cell tumors and abnormalities of the adjacent nonneoplastic cortex have been issued.
METHODS
The clinicopathologic features of 34 surgically resected ganglion cell tumors (32 gangliogliomas and 2 gangliocytomas) were retrospectively analysed, and immunohistochemical characteristics and malignant changes of neuronal cells and the usefulness of the MIB-1 (Ki67) indices for grading ganglion cell tumors and abnormalities of the adjacent normal cortex were investigated using various immunohistochemical studies.
RESULTS
According to the Daumas-Duport grading system, there were 24 (70.6%) grade II, 8 (23.5%) grade III, and two (5.9%) grade IV cases. Malignant transformation was present only in the glial (7 cases) or both glial and neuronal (3 cases) components. The MIB-1 indices were statistically significant (p<0.001): grade II was 0.0-1.05% (0.27+/-0.3%), grade III was 0.8-8.02% (2.8+/-3.2%), and grade IV was 3.0-4.99% (3.99+/-1.0). Anaplasia and MIB-1 positivity was observed among the neurons in the three cases. Perikaryal cytoplasmic expression or surface punctate accentuation of synaptophysin were noted only in the neoplastic neurons in some cases. Fifteen out of 20 cases, which included the nonneoplastic cerebral cortex, displayed mild cortical dysplasia (microdysgenesis).
CONCLUSIONS
The neuronal component also showed malignant transformations with proliferating activity. In our study, synaptophysin-immunoreactive patterns of neoplastic neurons were unique. The MIB-1 indices were helpful for grading ganglion cell tumos. Only mild cortical dysplasia was present in the normal cortex adjacent to the tumor.

The Expression of c-erbB-2, EGFR, p53 and Ki-67 in Ovarian Borderline Tumors and Carcinomas of the Ovary.: Kyueng Whan Min, Moon Hyang Park; Korean J Pathol. 2007;41(5):296-306.

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Abstract PDF: BACKGROUND
An ovarian surface epithelial tumor is a heterogenous disease, and various biological and molecular factors are important for its development and progression. Several findings support EGFR or c-erbB-2 as adverse prognostic indicators for an ovarian carcinoma.
METHODS
We reviewed the histological and clinical findings of 52 carcinomas (17 endometrioid, 16 serous, 13 mucinous and 6 clear cell tumors), and 26 borderline (10 serous and 16 mucinous) tumors. Expression of c-erbB-2, EGFR, p53, and Ki-67 was evaluated on paraffinembedded tissue from a primary ovarian tumor by immunohistochemical methods.
RESULTS
Expression of c-erbB-2 was found in 7.6% of tumors and expression of EGFR was found in 9.6% of tumors by immunohistochemical analysis. No significance was found between cerbB- 2 and EGFR expression as indicators of a poor prognosis. The expression of p53 and Ki-67 (>50%) correlated with the grade and type of tumor in the ovarian cancers. p53 and Ki- 67 overexpression (>50%) was absent in the borderline ovarian tumors, whereas ovarian carcinomas showed expression of both p53 and Ki-67.
CONCLUSION
Expression of c-erbB- 2, EGFR, p53, and Ki-67 as determined by immunohistochemical analysis did not correlate with prognostic significance. However, p53 and Ki-67 expression may be used as markers to predict aggressive behavior, and to differentiate between malignant and borderline epithelial ovarian tumors. Further large-scale studies are required to clarify the significance of c-erbB-2 and EGFR expression in ovarian tumors.

Case Report

Sinonasal Low-Grade Adenocarcinoma: Report of Three Cases with the Clinicopathologic and Immunohistochemical Findings.: Joon Seon Song, Shin Kwang Khang, Jooryung Huh, Bong Jae Lee, Kyung Ja Cho; Korean J Pathol. 2006;40(3):235-240.

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Abstract PDF: Low-grade adenocarcinomas that primarily arise within the sinonasal tract are uncommon tumors. We report here on three cases of primary sinonasal low-grade adenocarcinomas. The patients were 2 females and 1 male with ages of 48, 57 and 64, respectively. Microscopically, the tumors had a well developed tubulopapillary growth pattern that consisted of columnar or pseudostratified cells with eosinophilic cytoplasm, round to oval nuclei and rare mitotic activity. On immunohistochemistry, the tumor cells were strongly positive for cytokeratin 7, but they were negative for cytokeratin 20, CDX-2 and p53. The Ki-67 labeling index was very low (mean: 1.9%). Two patients developed recurrent tumors at the primary site after the initial surgery, but all the patients are presently alive without metastasis 6 years 8 months, 8 years 8 months, and 11 months after the initial diagnosis. When considering the progress of these tumors, we think that it's important to understand the pathology of this entity to avoid underdiagnosis because a complete excision is required for effective treatment.

Original Article

Altered Expression of DNA Topoisomerase IIalpha, Ki-67, p53 and p27 in Non-Hodgkin's Lymphoma.: Kyeong Min Lee, Mee Young Sol, Hyun Jeong Kang, Dong Hoon Shin, Kyung Un Choi, Hwal Woong Kim, Jee Yeon Kim, Do Youn Park, Chang Hun Lee; Korean J Pathol. 2005;39(5):332-337.

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Abstract PDF: BACKGROUND
Topoisomerase II (TOPO II) is an enzyme that separates intertwined chromosomes during DNA synthesis by transiently breaking and joining DNA strands. The level of TOP II is one of the determinants of cellular sensitivity to anti-tumor drugs in non-Hodgkin's lymphoma patients. The alpha form of TOPO II has been recently used as a marker of cellular proliferation. High levels of TOPO IIalpha are expressed in aggressive and proliferative tumors.
METHODS
This study was designed to evaluate the relationship between TOPO IIalpha expression and clinicopathological parameters including age, gender, the serum LDH level, the serum beta2-microglobulin level and stage, or expressions, of Ki-67, p53 and p27, in non-Hodgkin's lymphoma. We analyzed forty-one biopsied tissue specimens from patients with non-Hodgkin's lymphoma.
RESULTS
The expression of TOPO IIalpha increased with the clinical stage and it was correlated with Ki-67 and p53 expressions. However, TOPO IIalpha expression did not have any significant correlation with age, gender, the serum LDH level, the serum 2-microglobulin level and the p27 expression.
CONCLUSIONS
TOPO IIalpha expression is a useful marker of cellular proliferation and it may serve as a prognostic factor of a tumor's progression and aggressiveness in non-Hodgkin's lymphomas.

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