Journal of Pathology and Translational Medicine

Chang Soo Park

39 Articles

HPV Genotyping in Squamous Cell Carcinoma of Upper Aerodigestive Tract.: Young Kim, Eun Hui Jeong, Byung Woo Min, Sung Sun Kim, Yoo Duk Choi, Woon Jae Jung, Jong Hee Nam, Chang Soo Park; Korean J Pathol. 2010;44(5):483-487.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.483

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BACKGROUND
Smoking and alcohol consumption are the main risk factors for squamous cell carcinoma of the upper aerodigestive tract (SCCUAT). However, human papillomavirus (HPV) has been etiologically linked with tonsillar squamous cell carcinoma (TSCC). Therefore, we investigated the etiologic role of HPV in the context of SCCUAT in Korea.
METHODS
Archival paraffin block samples from 136 cases previously diagnosed as SCCUAT were randomly selected. A commercial HPV DNA chip was used for HPV genotyping.
RESULTS
One hundred and seventeen cases were available after checking beta-globin (47 cases of tonsil and 70 of non-tonsil). A HPV-positive result (HPV 16 and 18) occurred in 13 cases of SCCUAT, and 12 cases were tonsil (25.5%, 12/47). Among the 12 HPV-positive patients with TSCC, nine were non-smokers and non-drinkers. Most HPV-negative patients with TSCC had a history of alcohol drinking and smoking (32/35, 91.4%). HPV infection status was not significantly associated with histological grade, clinical stage, or survival in patients with TSCC.
CONCLUSIONS
HPV infection was significantly higher in patients with TSCC among those with SCCUAT. HPV may be independent risk factor in development of TSCC, such as smoking and alcohol drinking.

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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

Prognostic Value of Phosphorylated Akt and Survivin Expression in Gastric Adenocarcinoma.: Soong Lee, Yun Cheol Kim, Hyeon Min Lee, Ki Sang Lee, Byung Chul Shin, Hyung Seok Kim, Jae Hyuk Lee, Chang Soo Park, Kyung Hwa Lee; Korean J Pathol. 2010;44(3):252-258.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.252

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Abstract PDF

BACKGROUND
pAkt (the phosphorylated form of the proto-oncogene protein c-akt) and survivin (human BIRC5 protein) are candidate apoptosis-related molecules that may be responsible for cancer progression. The aim of this study was to determine the expression of pAkt and survivin in malignant stomach neoplasm, and their value as prognostic indicators of cancer.
METHODS
The expression of pAkt and survivin in 144 cases of gastric cancer was detected by immunohistochemistry and compared with established clinicopathological parameters and prognosis of this disease.
RESULTS
Expression of pAkt showed significant correlations with depth of invasion, lymph node and distant metastasis, as well as the stage (p < 0.05 for all three correlations), but not with the Lauren classification. Survivin expression closely correlated with histological type, Lauren classification, depth of invasion, metastasis, and stage (p < 0.05 for all). The overall survival of patients with pAkt/survivin expression was inferior to that of patients with loss of pAkt/survivin expression. Cox multivariate analysis demonstrated a significant correlation between stage (p = 0.04), survivin expression (p = 0.02), and prognosis.
CONCLUSIONS
Patients with pAkt/survivin expression in gastric cancer are at increased risk of cancer-related mortality via the apoptosis resistance pathway. Expression of pAkt and survivin could be used as a prognostic indicator for gastric cancer.

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Transcriptome analysis reveals GPNMB as a potential therapeutic target for gastric cancer
Feifei Ren, Qitai Zhao, Bin Liu, Xiangdong Sun, Youcai Tang, Huang Huang, Lu Mei, Yong Yu, Hui Mo, Haibin Dong, Pengyuan Zheng, Yang Mi
Journal of Cellular Physiology.2020; 235(3): 2738. CrossRef
The Relationship Between Estrogen/Progesterone Receptor and Expression of mTOR/pAkt Proteins and the Analysis of Prognosis in Breast Cancer
Sun Wook Han, Moon Soo Lee, Sung Yong Kim, Gil Ho Kang, Zi Sun Kim, Cheol Wan Lim, Ji Hyun Lee, Hyun Ju Lee, Mee-Hye Oh, Min Hyuk Lee
Journal of Breast Disease.2013; 1(1): 8. CrossRef
Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer
Mee-Hye Oh, Hyun Ju Lee, Seol Bong Yoo, Xianhua Xu, Jae Sung Choi, Yong Hoon Kim, Seok Yeol Lee, Choon-Taek Lee, Sanghoon Jheon, Jin-Haeng Chung
Virchows Archiv.2012; 460(6): 601. CrossRef

Metastatic Osteosarcoma to the Prostate: A Case Report.: Hyoung Yeon Seo, Jae Hyuk Lee, Chang Soo Park, Jin Gyoon Park, Sung Taek Jung; Korean J Pathol. 2009;43(5):475-477.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.475

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Abstract PDF: The most common site for the metastasis of osteosarcoma is the lung, and other sites of metastases include the bone, lymph node, pleura and liver. Although unusual extrapulmonary metastases have been reported with the improvement of the therapeutic results for the primary lesions, they are exceptionally rare. We report here on a case of prostatic metastasis of an osteosarcoma of the proximal tibia, and this developed seven years after successful resection, and four years after resection of a pulmonary metastasis. Radical prostatectomy was performed, and histological examination demonstrated metastatic osteosarcoma. To the best of our knowledge, this is the first case of prostatic metastasis of osteosarcoma in the medical literature.

Expression of Survivin in Gastric Carcinoma and its Relation to Tumor Cell Proliferation and Apoptosis.: Wan Sik Lee, Sung Bum Cho, Jong Sun Rew, Jae Hyuk Lee, Chang Soo Park, Young Eun Joo; Korean J Pathol. 2009;43(4):329-334.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.329

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Abstract PDF

BACKGROUND
Survivin, a novel antiapoptotic gene has been linked with tumor development and progression in various human carcinomas including gastric carcinomas. The aim of this study was to evaluate the expression of survivin in gastric carcinoma and its correlation with tumor cell proliferation and apoptosis. METHODS: Expression of survivin was evaluated immunohistochemically in 84 surgically resected gastric carcinomas. Tumor cell apoptosis was evaluated with terminal deoxynucleotidyl transferase (TdT) mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL), and Ki-67 immunostaining was used for evaluation of tumor cell proliferation. RESULTS: Expression of survivin was noted in 53.6% of the gastric carcinomas, and was significantly associated with depth of invasion, status of lymph node metastasis or tumor stage (p=0.022, 0.034, 0.040, respectively). There was an inverse correlation between survivin expression and apoptotic index (p=0.015). But there was no significant correlation between survivin expression and Ki-67 labeling index (p=0.430). CONCLUSIONS: These results suggest that survivin expression may contribute to tumor development and progression by inhibiting apoptosis in human gastric carcinoma.

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Significance of intracellular localization of survivin in cervical squamous cell lesions: Correlation with disease progression
SOO-AH KIM, RAN HONG
Oncology Letters.2014; 7(5): 1589. CrossRef

Analysis of HPV-other Samples by Performing HPV DNA Sequencing.: Yoo Duk Choi, Chang Woo Han, Woon Jae Chung, Woon Won Jung, Ji Shin Lee, Jong Hee Nam, Min Cheol Lee, Sang Woo Juhng, Ho Sun Choi, Chang Soo Park; Korean J Pathol. 2009;43(3):250-253.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.250

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Abstract PDF

BACKGROUND
HPV-other samples are designated as being positive on HPV-PCR, but negative when using specific HPV hybridization probes. We wanted to determine the types on the HPV-other samples by performing sequencing, and to know the pathologic status of the uterine cervix according to the HPV type detected on sequencing.
METHODS
For HPV genotying, we used the commercially available HPV DNA Chip test, which contains 15 types of high-risk HPV and 9 types of low-risk HPV. The HPV DNA sequencing was performed for the HPV-other samples of 209 patients who subsequently underwent cervical biopsy.
RESULTS
For 204 of the 209 samples, the HPV types detected by sequencing were absent types at used HPV DNA chip. For the remaining 5 samples, sequencing was impossible due to mixed peaks. HPV-81 (19.6%), HPV-61 (18.6%), HPV-62 (16.7%) and HPV-84 (13.9%) were frequently detected. For the HPV-81, -62, -71, and -72 samples, most of the samples displayed normal or LSIL. However, HPV-84 and -61 were more associated with HSIL or worse, as compared to the other types.
Conclusion
HPV-81, -61, -62 and -84 were frequently found on sequencing analysis of the HPV-other samples. The pathologic status was diverse, according to the HPV type detected on sequencing.

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Changes in microbial composition and interaction patterns of female urogenital tract and rectum in response to HPV infection
Yong-Hong Dong, Yu-Hua Luo, Chen-Jian Liu, Wen-Yu Huang, Lin Feng, Xing-Yuan Zou, Jin-Yan Zhou, Xiao-Ran Li
Journal of Translational Medicine.2024;[Epub] CrossRef
Cervical Dysplasia, Infection, and Phylogeny of Human Papillomavirus in HIV-Infected and HIV-Uninfected Women at a Reproductive Health Clinic in Nairobi, Kenya
Agnes Omire, Nancy L. M. Budambula, Leah Kirumbi, Hillary Langat, Danvas Kerosi, Washingtone Ochieng, Raphael Lwembe
BioMed Research International.2020; 2020: 1. CrossRef
Molecular characterisation of genital human papillomavirus among women in Southwestern, Nigeria
Yewande T. Nejo, David O. Olaleye, Georgina N. Odaibo, Jason Blackard
PLOS ONE.2019; 14(11): e0224748. CrossRef
Sequencing analysis of HPV-other type on an HPV DNA chip
Min-Jeong Kim, Jin Ju Kim, Sunmie Kim
Obstetrics & Gynecology Science.2018; 61(2): 235. CrossRef
Molecular epidemiology and genotype distribution of Human Papillomavirus (HPV) among Arab women in the state of Qatar
Devendra Bansal, Asha A Elmi, Sini Skariah, Pascale Haddad, Laith J Abu-Raddad, Aysha H Al Hamadi, Nady Mohamed-Nady, Nahla M Affifi, Randa Ghedira, Elham Hassen, Asma AJ Al-Thani, Afaf AHM Al-Ansari, Ali A Sultan
Journal of Translational Medicine.2014;[Epub] CrossRef
HPV Prevalence and Detection of Rare HPV Genotypes in Hong Kong Women from Southern China with Cytological Abnormalities
Ngai Na Chloe Co, Lai-On Chu, Joseph K. F. Chow, Joseph W. O. Tam, Enders K. O. Ng
ISRN Virology.2013; 2013: 1. CrossRef
Type-specific prevalence of high-risk human papillomavirus by cervical cytology and age: Data from the health check-ups of 7,014 Korean women
Min-Jeong Kim, Jin Ju Kim, Sunmie Kim
Obstetrics & Gynecology Science.2013; 56(2): 110. CrossRef

Progressive Multifocal Leukoencephalopathy in the Immunocompromised Patients - 3 Cases Report.: Min Keun Shim, Jo Heon Kim, Chang Soo Park, Hyung Seok Kim, Yoo Duk Choi, Min Cheol Lee; Korean J Pathol. 2007;41(5):358-361.

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Abstract PDF: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease resulting from infection of oligodendrocytes with JC virus. PML was a rare disease, but nowadays not uncommon as AIDS prevailed. Histopathologic features of the affected lesion shows infiltrations of foamy macrophages and hyperchromatic, pleomorphic, reactive astrocytes that may raise the suspicion of a brain tumor. We recently met with 3 cases of PML. Two of the patients had AIDS and the other had been treated for lymphoma. All cases were diagnosed by histopathologic examination in stereotactic brain biopsies.

Tetranucleotide Repeat Microsatellite Instability in Uterine Cervical Carcinomas.: Yoo Duk Choi, Ji Shin Lee, Chan Choi, Chang Soo Park, Sang Woo Juhng, Ho Sun Choi, Jong Hee Nam; Korean J Pathol. 2007;41(1):30-37.

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Abstract PDF: BACKGROUND
Elevated levels of microsatellite alterations at selected tetranucleotide repeat regions (EMAST) have been recently described, and they are a distinct type of microsatellite instability (MSI). We investigated the prevalence of EMAST in squamous cell carcinoma (SCC) of the uterine cervix and we determined the correlation between EMAST and the clinicopathologic parameters, HPV infection and the p53 mutation.
METHODS
We examined the 3 mono-, 3 di-, and 5 tetranucleotide repeat markers in 47 cases of SCC, and we performed immunohistochemical staining for p53. HPV detection and genotyping was performed using a commercially available HPV DNA chip.
RESULTS
Thirteen out of 47 cases (27.7%) were EMAST(+) with at least one of five tetranucleotide repeat markers. However, MSI at mono- and dinucleo- tide markers was noted in only one case (2.1%). EMAST was not related with stage, size, lymph node metastasis, vascular/lymphatic invasion or the depth of invasion. Positive immunostaining for p53 was significantly more common in EMAST(+) tumors than in the EMAST(-) tumors (p=0.04). HPV-infection was positive in 32 cases. EMAST was not correlated with the state of HPV infection state or the HPV genotype.
CONCLUSIONS
27.7% of the invasive SCCs of the uterine cervix exhibited EMAST, and EMAST in the SCC of the uterine cervix was significantly associated with the p53 mutation.

Evaluation of Self-collected Pad Sampling for the Detection of HPV In Cervicovaginal Secretion.: Seong Rim Kim, Sang Yong Song, Dae Shick Kim, Jung Won Lee, Chang Soo Park, Duk Soo Bae, Hyen Ji Lee, Kyung Tae Kim, Oh Joong Kwon, Eun Seop Song, Hee Jae Joo, Gheungwhan Ahn; Korean J Pathol. 2004;38(4):258-264.

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Abstract PDF: BACKGROUND
Self-collection of secretion samples for HPV testing is a feasible alternative method for women who would decline to participate in population based cervical cancer programs. The purpose of this study was to determine the sensitivity and specificity of self-sampling for HPV in determining high grade squamous intraepithelial lesion (HSIL) using the pad, and we also wished to compare the results from samples collected by women themselves and those results from samples collected by physicians.
METHODS
Fifty patients voluntarily participated in the sensitivity and specificity study at the university hospitals and 290 volunteers participated in the agreement study at local clinics. DNA was extracted and amplified using HPV L1 consensus primers for the direct sequencing of the pad samples.
RESULTS
For the detection of HSIL, self-collected pad sampling showed good sensitivity (75.0%) and excellent specificity (100%). Two hundreds eighty-six samples from the pads and concurrent physicians?samples showed the agreement at 98.6% with the Kappa, 0.9622 (p=0.0000).
CONCLUSIONS
A self-sampling method using the pad for the detection of HPV DNA is suggested to be an efficient method to access many women for screening easily, rapidly and conveniently. Testing the pad method? utility for a country- or large area-based mass screening study will be necessary in the future.

Stromelysin-3 Expression in Squamous Intraepithelial Lesions and Invasive Squamous Cell Carcinoma of the Uterine Cervix.: Yoo Duk Choi, Eun Jung Park, Jong Hee Nam, Chang Soo Park; Korean J Pathol. 2002;36(6):389-393.

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Abstract PDF: BACKGROUND
Matrix metalloproteinase (MMP) plays an important role in the invasion and metastasis of epithelial neoplasms. Currently, detected stromelysin-3 (ST-3) (MMP-11) is thought to be associated with invasiveness in epithelial neoplasms. However, the study of the expression of stromelysin-3 in the uterine cervix is yet to be delineated.
METHODS
Stromelysin-3 expression in cervical invasive squamous cell carcinoma (SCC) and in squamous intraepithelial lesions (SIL) having potentiality to become invasive was studied by immunohistochemical analysis. We examined the correlation between ST-3 expression and the histopathological parameters of the invasive carcinoma, including growth pattern, lymph node involvement, and degrees of differentiation.
RESULTS
The stromelysin expression rates were as follows; 8.3% in low grade SIL (LSIL), 18.9% in High grade SIL (HSIL), and 75.6% in SCC. A statistical difference in the expression difference was exhibited only between invasive SCC and SIL, but not between LSIL and HSIL, even though HSIL showed a higher expression rate than LSIL. No significant association was found in invasive SCC between ST-3 expression and histopathological parameters.
CONCLUSIONS
ST-3 expression is associated with tumor invasiveness in squamous lesions of the uterine cervix and not with histopathological parameters in invasive SCC.

Clonality Study in Carcinosarcomas and Malignant Mixed Epithelial Tumors.: Eun Jung Park, Yoo Duk Choi, Jong Hee Nam, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng, In Seon Choi, Kyung Hee Kim, Chan Choi; Korean J Pathol. 2002;36(4):205-211.

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Abstract PDF: BACKGROUND
Tumors are usually considered to be clonal progeny of single transformed cells. Carcinosarcomas and malignant mixed epithelial tumors are examples where controversies exist regarding the singularity or multiplicity of their cell of origin.
METHODS
The authors examined the clonality of carcinosarcomas (7 cases) and malignant mixed epithelial tumor (5 cases) in female patients by X-chromosome inactivation as a marker. Each component of the tumors were picked up by the laser capture microscope. The polymorphic exon 1 CAG trinucleotide repeat in the X-linked human androgen receptor (HUMARA) gene was amplified by a polymerase chain reaction before and after treatment of the methylation-sensitive endonuclease HpaII.
RESULTS
Eleven cases were informative for clonality determination. Six out of seven carcinosarcomas and three out of four malignant mixed epithelial tumors revealed the same patterns of X-chromosome inactivation, which suggests that they are monoclonal. In contrast, the patterns of X-chromosome inactivation were different between the two tumor components in each cases of carcinosarcoma and malignant mixed epithelial tumor, indicating that they are of polyclonal origin.
CONCLUSIONS
These observations show that although most of carcinosarcomas and malignant mixed epithelial tumors are of monoclonal origin, some of them are of polyclonal origin. This finding suggests that these tumors are genuinely polyclonal, and that they originated in the neoplastic transformation of more than one somatic cells

Mesoblastic Nephroma of Adulthood.: Jae Woo Park, Jae Hun Chung, Jae Hyuk Lee, Jong Hee Nam, Chan Choi, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 2001;35(6):551-554.

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Abstract: Mesoblastic nephroma is a benign neoplasm of the kidney, which is usually diagnosed during the first six months of life. Incidence in adults is exceedingly rare. We report herein a case of mesoblastic nephroma that occurred in the upper pole of the right kidney of a 39-year-old woman. It was a round mass measuring 3X3X2 cm in dimension. Microscopically, it consisted of uniform spindle cells with foci of hyalinization and dystrophic calcification. Tubular structures were entrapped in the tumor. Upon immunohistochemical staining, the spindle cells were found to be positive for smooth muscle actin, desmin, and vimentin. The epithelial cells of the entrapped tubules were positive for cytokeratin. On electron microscopic examination, the spindle cells demonstrated smooth muscle differentiation identified by indented nuclei, microfilaments beneath the cell membrane, dense bodies, and basal lamina-like materials.

Epidermal Growth Factor Receptor Expression and Cell Proliferation in Renal Cell Carcinoma.: Ji Shin Lee, Jong Jae Jung, Min Cheol Lee, Chang Soo Park; Korean J Pathol. 2000;34(4):273-279.

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Abstract PDF: The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein whose expression is a possible cause of increased tumor cell proliferation and has recently been proposed as a prognostic parameter in some tumors. Expression of EGFR was studied immunohistochemically in 62 cases of human renal cell carcinomas to evaluate their possible prognostic roles. We also examined the correlation between EGFR expression and cell proliferation by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). Fifty-six cases (90.3%) expressed EGFR, with staining largely confined to the cell membrane and cytoplasm. Staining intensity of EGFR was directly correlated with nuclear grade (p=0.000) and TNM stage (p=0.015). PCNA index was significantly higher in EGFR-positive tumors than in EGFR- negative tumors. There was a statistically significant positive correlation between PCNA index and increasing staining intensity of EGFR (p=0.000). In univariate survival analysis, EGFR expression was significantly associated with shortened survival. However, EGFR expression was not an independent prognostic factor by multivariate analysis. These findings suggest that EGFR expression may be an important cause of tumor cell proliferation in renal cell carcinoma and further studies are needed to evaluate whether EGFR expression analysis provides independent prognostic information.

Tumor Angiogenesis in Renal Cell Carcinoma.: Ji Shin Lee, Jong Jae Jung, Chang Soo Park; Korean J Pathol. 1999;33(11):1055-1060.

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Abstract PDF: Angiogenesis is essential for the growth of solid tumors. Microvessel counts, which represent a measure of tumor angiogenesis, have been correlated with the overall survival of patients with a variety of malignancies. However, the significance of angiogenesis in renal cell carcinoma remains controversial. To determine whether angiogenesis correlates with prognosis of patients with renal cell carcinoma, we counted the microvessels within the primary tumors and compared their numbers with patients' prognosis. Tumor specimens from 42 patients were investigated. Microvessels were stained with anti-CD34 and anti-factor VIII-related antigen monoclonal antibodies. Significant correlation between microvessel counts for two antibodies was observed (r=0.875, p<0.01), although microvessel counts for CD34 were approximately two times higher. Microvessel counts were higher in clear cell than in non-clear cell carcinoma (p<0.05). These results suggest that immunostaining with anti-CD34 antibody may provide a more sensitive and accurate measure of tumor angiogenesis. There was no correlation between microvessel counts and nuclear grade, or TNM stage. In univariate analyses, nuclear grade and TNM stage were significantly associated with patient survival (p<0.01). But further studies on tumor angiogenesis of renal cell carcinoma are needed before it can be adopted as a prognostic marker.

Morphometric Study for Muscular and Microvascular Remodeling of Left Ventricular Free Wall and Interventricular Septum in Hypertrophic Cardiomyopathy.: Young Jik Lee, Hyung Suk Kim, Jong Tae Park, Chang Soo Park; Korean J Pathol. 1999;33(9):675-683.

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Abstract PDF: Hypertrophic cardiomyopathy (HCMP) is characterized myofiber hypertrophy and structural remodeling with changes in the proportion of the muscular, vascular, and interstitial compartments. A study was done to determine the structural remodeling patterns and the role of microvasculature of hearts in HCMP. Forty-two postmortem hearts were analyzed including 14 from patients who died of HCMP (group 1), 8 patients with HCMP but who died from extracardiac causes (group 2), 10 patients with ischemic heart disease (group 3), and 10 normal adult hearts (group 4). Macro- and microscopic examination, immunohistochemical study using CD34 antibody, and morphometric studies using image analyzer were performed. Mean cardiac weight and wall thickness were significantly higher in the HCMP group. Myocardial hypertrophy, and a variety of myocardial disarray and fibrosis involved the whole area of the left ventricles with HCMP. The percentage areas of microvessels were 6.40 0.7 in group 1, 5.90 0.6 in group 2, 4.98 0.3 in group 3, 4.85 0.4 in group 4, respectively, and the numbers of microvessels were 198.0 20.7 in group 1, 230.0 22.3 in group 2, 211.7 11.2 in group 3, and 236.4 11.4 in group 4, respectively (mean SE). The percentage area of microvessels was significantly higher in group 1 than in other groups. However, the number of microvessels in that group was lower than in the other groups, although it was statistically insignificant. Since flow-dependent vasodilation is preserved in HCMP, we considered flow-dependent vasodilation the cause of the discrepancy between the area and the number of microvessels. Ischemic changes observed in chronic HCMP and related heart failure were considesed to be due to the relative deficiency of the coronary flow compared to the increasing cardiac mass.

Relationship between Insulin Secretory Capacity and Mitochondrial Morphology in Pancreatic beta-Cell.: Seung Won Yang, Jae Hyuk Lee, Chang Soo Park, Min Young Chung; Korean J Pathol. 1999;33(5):326-336.

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Abstract PDF: To investigate the relationship between insulin response and morphometric changes of the mitochondria of pancreatic beta-cell, this study was performed using hyperglycemia and streptozotocin as oxidative stresses. Adult and neonatal rats were used. Intravenous glucose tolerance test (IVGTT) and morphologic examination of pancreas using immunohistochemical stain, in situ end-labeling method and electron microscopic study were performed. Various mitochondrial parameters were measured by image analyzer. Immunohistochemical stain revealed a markedly reduced islet size and decreased number of beta-cells and the increased number of non-beta-cell in adult and neonatoal streptozotocin group, and the appearance of insulin positive cells throughout the exocrine parenchyma in neonatal streptozotocin group. Three days after injection of streptozotocin in adult streptozotocin group, TUNEL stain showed increased apoptotic cells in islets. Ultrastructurally, beta-cells in adult streptozotocin group showed increase in number and size of mitochondria, and disruption of mitochondrial structures. Hyperglycemic group and neonatal streptozotocin group showed preserved mitochondrial ultrastructure. Ultrastructural morphometric study revealed increase in size and number of mitochondria and decrease in mitochondrial contour index in adult streptozotocin-treated rats, which suggested mitochondrial degeneration. Hyperglycemic group showed mild increase in size of mitochondria. Increased number of mitochondria was also observed in neonatal streptozotocin group. IVGTT revealed marked decrease in insulin response in adult streptozotocin group, and non-insulin-dependent diabetes mellitus pattern in glucose and insulin response in neonatal streptozotocin group. Hyperglycemic group showed a glucose and insulin response similar to control group. The above results suggest that a severe oxidative injury may cause degeneration and disruption of mitochondria of pancreatic beta-cell, and may be associated with substantial apoptotic cell death. The changes in the morphology and the number of mitochondria may result from streptozotocin treatment within neonatal period and hyperglycemia treatment, which may be associated with changes in insulin response.

Expression of Proliferating Cell Nuclear Antigen and p53 Protein in Ovarian Epithelial Tumors.: Jong Jae Jung, Jong Hee Nahm, Chang Soo Park; Korean J Pathol. 1998;32(3):193-200.

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Abstract PDF: p53 gene mutation is commonly accepted to be associated with loss of negative cell cycle control and progression of tumors. The proliferative activity of tumor cells is considered to be a valuable indicator of tumor aggressiveness. This study is intended to compare p53 protein expression with cell proliferation rates in the ovarian epithelial tumors according to the various clinicopathological parameters. Immunohistochemistry using monoclonal p53 antibody (DO-1) and PCNA antibody (PC10) was applied to 56 cases of ovarian epithelial tumors including 17 cases of borderline tumor. The results were as follows. Both immunohistochemical staining of PCNA and p53 protein showed positive reactions confined to the nuclei of tumor cells. There were significant differences of p53 protein expression rates between borderline malignancies (11.8%) and cystadenocarcinomas (56.4%) of ovary. The expression rate of p53 protein was not significantly different according to the differentiation and the stage, but the cases of strong positive reaction to p53 protein were more frequently noted in the poorly differentiated and advanced staged tumors. The PCNA indices of p53 strong positive cases were higher than those of p53 weak positive cases. In summary, p53 protein and PCNA expression may be used as an adjuvant in differentiating borderline lesions from carcinomas of ovary and predicting their biological behaviors.

A Comparative Study of Immunohistochemistry and PCR-SSCP for Detection of p53 Mutation In Gastric Carcinoma.: Jong Soon Kim, Jae Hyuk Lee, Min Cheol Lee, Chang Soo Park, Sang Woo Juhung; Korean J Pathol. 1998;32(1):21-28.

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Abstract PDF: Mutation of the p53 tumor-suppressor gene in exons 4 through 9 was examined in 34 cases of primary advanced gastric cancer using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) and the results were compared with p53 protein expression as determined by immunohistochemistry (IHC) using a monoclonal antibody(DO-1). p53 protein detected by IHC was observed in 14 cases (41.2%) and genotypic mutation detected by PCR-SSCP in exons 4-9 was observed in 13 cases (38.2%) One case showed an aberrant band on PCR-SSCP both in Exon 7 and Exon 8/9. p53 alteration detected by either IHC or PCR-SSCP was observed in 19 cases (55.9%), but only 8 cases (23.5%) showed both p53 mutation and protein expression. We also tried to obtain the correlation between relative intensity of the shifted bands on PCR-SSCP and percentage of positive cells by IHC, but a significant correlation was not seen between relative intensity of shifted bands on PCR-SSCP and positve cell ratio. A discrepancy between p53 protein expression and p53 mutation is observed in primary gastric carcinomas. The reason for this discrepancy are not apparent. However, examination of gastric carcinomas for mutations in other exons may identify a better correlation with protein overexpression. The results obtained in this study suggest that the negative reaction for p53 immunohistochemistry may not necessarily mean no genetic alteration of the p53 locus.

Microsatellite Instability and the Expression of Tumor-associated Genes in Multiple Cancer.: Kyung Soo Kim, Chan Choi, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 1997;31(7):617-627.

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Abstract PDF: Genetic changes associated with oncogenes or tumor suppressor genes are frequently observed in human cancers. These changes may be more frequent in multiple primary cancers than sporadic cancers. These experiments were designed in order to know the genetic changes using microsatellite PCR technique and the expression of tumor-associated genes by immunohistochemistry for c-myc and p53 in 17 cases of multiple primary carcinomas. The niicrosatellite instability (MSI) were found in 8 of 17 cases (47.1 %); six cases showed MSI in more than two microsatellite loci and two cases revealed MSI in one locus. MSI was found in 2 out of 7.patients (28.6%) of multiple primary carcinomas arising from the unrelated organs, and 6 out of 10 patients (60.0%) arising from the same or related organs. When each case of multiple primary carcinomas was examined, immunohistochemistry for c-myc was positive in 25 cases (71.4%) and p53 was positive in 21 cases (60.0%) out of 35 cases. But there was no correlation between MSI and expression of tumor-associated genes. From the above the results, MSI is more important in carcinogenesis of multiple primary carcinomas arising from the same or related organs than those from unrelated organs.

Detection of Human Papillomavirus in Lesions of Uterine Cervix Immunohistochemistry and in situ Hybridization.: Chang Soo Park, Jong Hee Nam, Jae Hyuk Lee, Jong Soon Kim, Seung Jin Oh; Korean J Pathol. 1997;31(4):289-297.

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Abstract PDF: To evaluate the detection of HPV DNA according to subtype of lesions of uterine cervix and its clinical applicability, in situ hybridization (ISH) and immunohistochemistry for HPV were performed in 189 cases of uterine cervical lesion, including 23 cases of low grade squamous intraepithelial lesion (SIL), 115 cases of high grade SIL and 51 cases of invasive carcinoma. Positive immunostaining, brown precipitate, was mainly noted in the nucleus of koilocytes in the superficial and intermediate layer. Positivity of immunostaining was 21.7% in low grade SIL, 13.0% in high grade SIL and 9.8% in invasive carcinoma. Positive reaction in ISH, red precipitate, was noted in the nucleus of not only koilocytes but also non-koilocytes in the superficial and intermediate layer, and dot precipitate was rarely identified in the nest of squamous cell carcinoma. Based on HPV subtype, 6/11 was 21.7% in low grade SIL, 16/18 was 32.2% and 39.2% in high grade SIL and invasive carcinoma, respectively. With regard to their associated HPV types, low grade SILs were heterogeneous and high grade SILs and invasive carcinomas were related with the high oncogenic risk group only. The correlation of HPV subtypes with panHPV was 91.3% in low grade SIL, 91.3% in high grade SIL and 98.0% in invasive carcinoma. These results suggest that detection of HPV infection by ISH may be a more useful method than immunohistochemistry and application of the HPV subtype probe with the panHPV probe could improve the sensitivity of ISH.

A Study on the DNA Ploidy and Expression of c-erbB-2 Oncogen in the Ovarian Carcinomas.: Jong Jae Jung, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 1997;31(1):15-22.

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Abstract PDF: To evaluate the relationships among the c-erbB-2 oncogene expression, DNA ploidy and other prognostic factors, an immunohistochemical study of the c-erbB-2 oncogene product and flow cytometric analysis of DNA ploidy were performed in paraffin sections of 42 cases of ovarian carcinomas. The results were as follows: 1) The positive reaction for c-erbB-2 oncogene product was observed mainly along the cytoplasmic membrane, and occasionally within the cytoplasm of the tumor cells. 2) Overall the positivity of c-erbB-2 oncogene expression was 45.2% of the ovarian carcinomas. By the histological types, the positivity was 35.7% in serous carcinoma, 80.0% in mucinous carcinoma, and 45.2% in endometrioid carcinoma; by the degree of differentiation, 57.1% in well differentiated carcinoma, 40.0% in moderately differentiated, and 27.3% in poorly differentiated; by the nuclear grading, 58.3% in grade I, 52.6% in grade II, and 18.2 % in grade III; and by the clinical staging, 57.1% in stage I, 42.8% in stage II, and 35.0% in stage III. The expression of the c-erbB-2 oncogene in the ovarian carcinomas was higher in the tumors of good differentiation, of the lower nuclear grade and of the lower clinical stage. 3) The incidence of DNA aneuploidy in the cases positive for the c-erbB-2 oncogene expression(47.3%) was higher than that in the negative cases(31.4%). From the above results, therefore, it is suggested that the c-erbB-2 oncogene may be involved in the early stage of ovarian carcinogenesis. Also suggested is that ovarian carcinomas positive for the c-erbB-2 oncogene in the early stages may have higher probability of having a DNA aneuploid cell line during the progress of the tumors.

The Study of p53 Expression and DNA Ploidy in Colorectal Carcinoma.: Ji Shin Lee, Kwang Soo Cheon, Chang Soo Park; Korean J Pathol. 1996;30(9):775-783.

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Abstract PDF: Mutation of the p53 gene frequently results in overexpression of the p53 protein and loss of its tumor-suppressing properties. The overexpression of the p53 gene could be an indicator of rapid proliferation, poor differentiation, advanced stages, or poor prognosis. The prognostic value of the overexpression of the p53 gene in colorectal carcinoma is equivocal. The presence of DNA aneuploidy has been described as a powerful adverse prognostic indicator in relation to survival. To investigate the prognostic significance of p53 expression, and the relationship with DNA ploidy, 92 cases of colorectal carcinomas were analyzed. The overexpression of p53 gene product was present in 50(54.4%) of 92 cases. p53 expression only correlated with recurrence or metastasis during the follow-up periods (p=0.045). DNA aneuploidy was observed in 32(39.1%) of 82 cases. DNA ploidy was strongly associated with lymph node invasion(p=0.005), Dukes' stage(p=0.003), TNM classification (p=0.003), and recurrence or metastasis during the follow-up periods (p=0.045). The frequency of DNA aneuploidy was higher in the p53-positive colorectal carcinomas(58.3%) than in the p53-negative colorectal carcinomas (21.6%) (p=0.003). p53-positive colorectal carcinomas had a higher rate of cell proliferation than p53-negative cases(p<0.001). These results suggest that checking the p53 expression and DNA ploidy could be useful prognostic indicators of colorectal carcinoma.

Diagnostic Value of p53 Expression in the Evaluation of Effusions.: Jin Shin Lee, Chang Soo Park; Korean J Cytopathol. 1996;7(2):138-143.

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Abstract PDF: The diagnostic accuracy of routine cytological preparations from effusions ranges from 60% to 70%. Immunohistochemical markers, especially tumor-associated antigens, have been successfully employed to increase diagnostic sensitivity in effusion cytology. However, more than two different antibodies in diagnosis of effusions are needed. In the view of prevalence of abnormalities of p53 gene in human malignancies, we investigated the diagnostic usefulness of demonstration of p53 protein immunoreactivity in distinguishing benign changes versus malignant processes in effusions. p53 protein expression was studied immunohistochemically in 76 effusions(28 malignant and 48 benign) using anti-human p53 antibody. p53 immunoreactivity was identified in 19 of 28(67.9%) malignant effusions. In contrast, no p53 immunoreactivity was!, observed in all benign effusions. A specificity of 100% and a sensitivity of 67.9% Were observed. These results suggest that immunohistochemical detection of p53 protein seems to be helpful in distinguishing benign changes versus malignant processes in effusions, although its principal limitation is-its relatively low sensitivity.

In Situ mRNA Hybridization and an Immunohistochemical Study of EGFR in Uterine Cervix Cancer.: Hyang Mi Ko, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 1995;29(3):343-351.

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Abstract PDF: Epidermal growth factor receptor (EGFR) is an intergral membrane protein. Overexpression or mutation of EGFR may play a role in careinogenesis. Recently, many molecular biologic techniques have been used to study expression of oncogenes. One of them, in situ mRNA hybridization, using paraffin embedded blocks, offers a unique means to allow precise localization within histological preparations, and also overcomes problems relating to translation defects and abnormal translation. In order to confirm the usefulness of epidermal growth factor receptor as a tumor marker, and to compare the expression of EGFR between in situ MRNA hybridization and an immunohistochemical study, in situ MRNA hybridization was performed along with an immunohistochemical study for EGFR in paraffin sections of 84 uterine cervix carcinomas. A positive reaction for EGFR was observed mairdy in the cytoplasm of tumor cells. The vascular muscle layer and uterine muscle tissue around the cancer nest revealed a positive reaction in immunohistochemical stain for EGFR, with a negative reaction for EGFR mRNA. In the cancer nests, the immunohistochemical positive reaction for EGFR was strong in differentiated cells and keratin pearls, but a strong positive reaction for EGFR mRNA was localized in undifferentiated cells. The overall positive of immunostaing for EGFR was 77% for uterine cervix carcinoma; 71 % for carcinoma in situ, 71 % for microinvaseve carcinoma, and 89% for invasive carcinoma. The overall positivity of EGFR from in situ MRNA hybridization was 94% of the uterine cervix carcinoma; 93% for carcinoma in situ, 93% for microinvasive carcinoma, and 96% for invasive carcinoma. From these results, EGFR is a useful tumor marker for uterine cervix carcinoma, and in situ mRNA hybridization has greater sensitivity and specificity than immunohistochemistry.

Immunohistochemical Evaluation of HMB-45 and S-100 Protein in Melanocytic Tumors.: Chang Soo Park, Hwan Kim, Hyang Mi Ko, Kyung Soo Kim, Ji Shin Lee; Korean J Pathol. 1995;29(2):189-196.

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Abstract PDF: Immunohistochemical staining on paraffin sections for S-100 protein improved diagnostic accuracy for melanocytic tumor. But specificity of S-100 protein in the diagnosis of melanocytic tumor is very low, because S-100 protein was also expressed in neurogenic tumor and salivary gland tumor. To investigate a specific tumor marker for the malignant melanoma, immunohistochemical staining for HMB-45 and S-100 protein was performed on the paraffin sections of 25 cases of malignant melanoma and 46 cases of nevi. Positive reaction for HMB-45 and S-100 protein was diffusely identified in the cytoplasm of tumor cells. Positive ratio for HMB-45 was 100% in malignant melanoma, 92% in junctional component of compound nevus and 0% in intradermal nevus. Positive ratio for S-100 protein was 92% in malignant melanoma, 100% in compound nevus and 100% in intradermal nevus. The sensitivity and specificity for HMB-45 in malignant melanoma were 100%, but those for S-100 protein were 92% in sensitivity and 86.7% in specificity. These results indicate that HMB-45 has a high sensitivity and specificity for malignant melanoma cells and it can be quite useful for the histopathological diagnosis of malignant melanoma.

A Study of the Correlation between Expression of c-erbB-2 Oncoprotein and Various Clinicopathological Prognostic Factors in Breast Carcinoma.: Jong Hee Nam, Kyung Soo Kim, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 1995;29(2):136-144.

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Abstract PDF: Immunohistochemical study for c-erbB-2 oncoprotein was performed on paraffin sections of 76 primary breast carcinomas to determine the relationship between expression of c-erbB-2 and various clinicopathological prognostic indicators, including the expression of epidermal growth factor receptor (EGFR). Positive reaction for c-erbB-2 oncoprotein revealed an intense red granular staining predominantly located at the tumor cell membrane, with some cells exhibiting a weak cytoplasmic staining as well. The epithelial cells of the normal lobule and duct showed a negative reaction. Positive reaction for EGFR revealed a granular staining in the cytoplasm and the cell membrane of the tumor cells. Some tumors showed a positive EGFR staining in the epithelial cells of normal duct and lobule. Twenty six of 76 cases (34.2%) of primary breast carcinomas revealed a positive reaction for c-erbB-2 oncoprotein, and 28 cases (36.8%) were positive for EGFR. Expression of c-erbB-2 oncoprotein and EGFR was evident in 37.7% and 40.6% of 69 classic invasive ductal carcinomas, respectively. None of the other histological types showed a positive reaction. Expression of c-erbB-2 oncoprotein was strongly associated with tumor size(p=0.0015), histologic grade(.p=0.0175), vascular invasion(p=0.0043), and lymph node metastasis(p=0.0024), but not with age at diagnosis(p=0.1836). No significant association was found between expression of c-erbB-2 oncoprotein and EGFR. Co-expression of c-erbB-2 oncoprotein and EGFR was also strongly associated with tumor size (p=0.0029). These results suggest that c-erbB-2 oncoprotein is biologically distinct from EGFR, and may be used as a prognostic indicator of breast carcinoma due to its strong association with various clinicopathological prognostic factors.

Cytomegalovirus Infection In a Patient with Hypersensitivity Angiitis due to H-S Purpura: A case report.: Ji Shin Lee, Hyang Mi Ko, Kyung Soo Kim, Chang Soo Park, J Sang Woo uhng; Korean J Pathol. 1995;29(1):119-121.

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Abstract PDF: Gastrointestinal cytomegalovirus(CMV) infection in adults is observed as a part of a generalized or localized infection in patients who are immunocompromized. We report a case of CMV infection of the small intestine. The patient is a 34 year-old woman who has complained of palpable purpura in the lower extremities and buttocks, and arthralgia of large joints. The skin biopsy showed fibrinoid necrosis and neutrophils with leukocytoclasis, which findings are compatible with hypersensitivity angiitis. The patient received steroid and cyclophosphamide. During the follow-up period, generalized edema and bloody stool were detected. Resected specimen of small bowel has multiple aphthous ulcer. Microscopically, cytomegalic cells are observed along the endothelial cells and mesenchymal cells. In situ hybridization using DNA probes against CMV revealed positive staining in the cytomegalic inclusions in vascular endothelial and mesenchymal cells.

DNA Ploidy in Anaplastic Carcinoma of the Thyroid Gland by Image Analysis.: Ji Shin Lee, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng; Korean J Cytopathol. 1995;6(1):10-17.

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Abstract PDF: Anaplastic carcinoma of the thyroid gland is one of the most malignant tumors. Recently, DNA ploidy measured by flow cytometry and image analysis has been suggested as an additional useful indicator of tumor behavior. Studies on the occurrence and clinical significance of DNA aneuploidy in anaplastic carcinoma of the thyroid are rare. In this study, the pattern of DNA ploidy was measured by image analysis on Papanicolaou stained slides in four cases of anaplastic carcinoma and also measured by flow cytometry using paraffin blocks in two cases. In all cases of anaplastic carcinoma. DNA aneuploidy was found by image analaysis. By flow cytometry, one case had a diploid peak and the other case had an arieuploid peak. According to the above results, we conclude that anaplastic carcinoma of the thyroid glands have a high incidence of DNA aneuploidy and image analysis using Papanicolaou stained slides is a useful method in detecting DNA aneuploidy.

Cytopathologic Features of Primary Bronchial Adenoid Cystic Carcinoma: A Case Report.: Ji Shin Lee, Jong Soon Kim, Bok Sook Yang, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng; Korean J Cytopathol. 1995;6(1):67-70.

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Abstract PDF: Adenoid cystic carcinoma arising from the submucosal glands of the trachea and bronchial tree is rare. The histopathology and natural history of bronchial adenoid cystic carcinoma have been well documented, but detailed descriptions of its cytomor- phology are few. We report a case of primary bronchial adenoid cystic carcinoma in a 20-year-old female, diagnosed by bronchial brushing cytology. The cytologic specimens showed large clusters of small cells arranged around cystlike spaces containing globular basophilic material.

The Study of Proliferating Cell Nuclear Antigen (PCNA) Reactivity in Fibrohistiocytic Tumors.: Jae Hyuk Lee, Yong Han Park, Hyang Mi Ko, Ji Shin Lee, Chang Soo Park; Korean J Pathol. 1994;28(4):350-357.

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Abstract PDF: Fibrohistiocytic tumors are a diverse group of benign and malignant soft tissue lesions, including dermatofibroma, dermatofibrosarcomaprotuberans, and malignant fibrous histiocytoma. On the clinical point of view, the distinction between benign and malignant lesions and malignancy grading is far more important. Therefore, we investigated 23 fibrohistiocytic tumors, using PCNA (PC10) which was a useful marker of proliferating activity, to differentiate the benign lesions from the malignant and correlate with other prognostic factors including tumor necrosis. cellularity, histologic grade, and mitotic counts. The results obtained were as follows 1) Positive tumor cells were clearly identified by the characteristic diffuse or granular nuclear staining. 2) The number of PCNA-positive tumor cells were 2.16+/-2.39% in dermatofibroma, 16.12+/-7.38% in dermatofibrosacoma protuberans, and 28.02+/-17.47% in the malignant fibrous histiocytoma. The numbers of PCNA-positive tumor cells in the malignant lesions higher than in the benign (p<0.001). 3) Deep seated, large size (>5 cm) and recurred or metastatic cases of MFH were more the high PCNA index (more than 20%) than the low index (less than 20%) groups. 4) PCNA index in MFHs had positive correlation with the number of mitotic counts (r=0.7582, p<0.001), cellularity (r=0.5908, p<0.05) and histologic grade (r=0.4164, p<0.05). These results suggested that reactivity on PCNA might assist in the distinction between benign and malignant lesions in fibrohistiocytic tumors, and could be a useful prognostic factor in the patients with malignant fibrous histiocytoma.

Fine Needle Aspiration Cytology of Anaplastic Carcinoma with Osteoclastlike Giant Cells of the Thyroid.: Ji Shin Lee, Hyang Mi Ko, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng; Korean J Cytopathol. 1994;5(2):172-175.

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Abstract PDF: Anaplastic carcinoma of the thyroid is one of the most malignant tumors and survival for longer than three years after diagnosis is exceptional. Multinucleated giant cells of osteoclastlike appearances are seen in some of the anaplastic carcinoma, but only three cases in which the diagnosis was made by fine needle aspiration(FNA) cytology are reported in the international literature. We experienced a case of anaplastic carcinoma with osteoclastlike giant cells in a 66-yr-old female, diagnosed by FNA cytology. The smears revealed two cell populations; multinucleated giant cells and large polygonal or spindle shaped malignant cells. The FNA cytodiagnosis of anaplastic thyroid carcinoma containing osteoclastilke giant cells was substantiated by subsequent biopsy.

A Case of Orbital Meningioma Diagnosed by Fine Needle Aspiration Biopsy.: Ji Shin Lee, Kyung Soo Kim, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng; Korean J Cytopathol. 1994;5(2):176-179.

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Abstract PDF: Orbital meningioma is a rare neoplasm that, even when suspected by CT or echographic examination, requires careful histologic study for precise identification. Fine needle aspiration(FNA) biopsy has become the diagnostic technique of choice in recent years for investigating orbital masses. There have been a few previous reports on FNA biopsy of orbital menigioma. We experienced a case of orbital meningioma in a 11-yr-old boy, diagnosed by FNA biopsy. The cytohistologic features of aspirated material(intranuclear inclusions. psammoma bodies, and cells arranged in whorls) made it easy to diagnose a meningioma.

Correlation between Expression of c-erbB-2 Oncogene and Various Prognostic Factors in the Colorectal Carcinoma.: Wan Kim, Hong Ran Choi, Ji Shin Lee, Jong Tae Park, Chang Soo Park, Kyu Hyuk Cho; Korean J Pathol. 1993;27(3):217-225.

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Abstract PDF: The c-erbB-2 oncogene, which is a new human proto-oncogene similar to EGFR structurally, generates a glycoprotein of tyrosine kinase family with a molecular weight of 185,000 To evaluate the prognostic significance of c-erbB-2 oncogene expression in colorectal carcinoma, We analysed 73 colorectal carcinomas in paraffin sections immunohistochemically, using the monoclonal antibody specific for the c-erbB-2 oncogene product and correlated with clinicopathological data. The results were as follows 1) The immunoreactivity for c-erbB-2 oncogene was localized to cell membrane of the tumor cells and occasionally observed within the cytoplasm. 2) The positivity of c-erbB-2 oncogene expression was 71.2%(52/73) of the colorectal carcinomas overall. According to the histological types, the positivity of c-erbB-2 oncogene in adenocarcinoma(77.4%) was higher than that in mucinous carcinoma(36.4%)(p<0.05). 3) Expression of c-erbB-2 oncogene was significantly correlated with lymph node metastasis or distant metastasis(p=0.0117), Dukes stage(p=0.0432), and TNM classification(p=0.0102). These results suggest that c-erbB-2 oncogene expression may be used as a prognostic factor of colorectal carcinoma because of its correlation with other clinicopathological prognostic factors.

Discriminant Analysis of Tumor Cell Subpopulation Based on Morphometric and Photometric Features: Observations on tumor cells of the uterine cervix carcinoma.: Chang Soo Park, Dae Yong Choi, Min Cheol Lee, Sang Woo Juhng; Korean J Pathol. 1993;27(2):108-114.

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Abstract PDF: DNA aneuploid cells are poorly characterized in both biochemical and morphological terms. This study was performed to see the relationship between DNA ploidy and morphometric and photometric nuclear features. DNA contents of tumor cells were measured by image cytometry in 46 cases of micro- or early invasive squamous cell carcinoma of the uterine cervix. Also measured were nuclear area, perimeter, maximum diameter, chromatin pattern index, and staining intensity. Among the 46 cases, 20 cases which had both DNA diploid and aneuploid cell subpopulations were selected, and the two subpopulations were discriminated statistically. Multivariate discriminant analysis seperated clearly the two subpopulations, whereas univariate analysis failed. For canonical discriminant function, nuclear area was selected first, followed by staining intensity in each case. Other variables selected afterwards were nuclear perimeter, maximum diameter, and/or chromatin pattern index in random fashion. Correlation coefficient between the canoncial discriminant function and the variables were 0.20~0.40 for nuclear area and 0.25 or less for the others. The above results suggest that DNA ploidy is a parameter more or less independent on individual morphometric and photometric parameters.

Immunohistochemical and Ultrastructural Cellular Differentiation in Papillary and Solid Epithelial Neoplasm of the Pancreas.: Jae Hyuck Lee, Min Cheol Lee, Chang Soo Park, Kyu Hyuk Cho; Korean J Pathol. 1992;26(1):40-52.

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Abstract PDF: Papillary and solid epithelial neoplasm of the pancreas from five patients were studied using immunohistochemistry and electron microscopy to define the cellular origin of this type of tumor. The tumors ranged in diameter form 5.5 to 15 cm Grossly, these were well circumscribed by a firm, gray-white, fibrous capsule and their cut-surface showed mainly area containing mucinous substance with necrotic and hemorrhagic material, with some solid portion. Microscopically, there was a solid and papillary pattern, with uniform cells typically having round to ovoid nuclei containing indistinct nucleoli and eosinophilic, granular cytoplasm. Within the cytoplasm of the tumor cells, numerous PAS-positive granules were found. Immunostaining was positive for neuron-specific enolase(three of five cases), alpha1-antitrypsin and alpha1-antichymotrypsin(three of five cases) in the solid and papillary portion of the tumor. But no polypeptide hormone immunoreactive cells were present in all cases except for gastrin which showed focally weak positivity in the papillary area. Ultrastructurally, the papillary and solid epithelial neopasm of the pancreas showed evidence of acinar cell differentiation, because in the cell of one observed some zymogen-like granules and presence of annulate lamellae. But also, abundant typical neurosecretory granules were detected in the tumor cells ultrastructurally. Both facts suggested acinar and islet cell differentiation of the tumor. From the these findings, it concluded that papillary and solid epithelial neoplasm of the pancreas may be originated from a primordial cell which will be able to render both endocrine and exocine component.

The Expression of ras Oncogene in Benign and Malignant Lesions of Breast.: Jong Hee Nahm, Jong Hyun Lee, Chang Soo Park, Kyu Hyuk Cho; Korean J Pathol. 1989;23(1):85-93.

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Abstract PDF: To evaluate correlation between the amount of oncogene products in tumor cell extracts and malignant potentiality in breast tumor, immunohistochemical staining for the ras Oncogene products was performed in the sections of benign and malignant lesions of the breast. The results obtained were as follows: 1) The positive reaction to ras Oncogene products was usually observed in the cytoplasm and cell membrane. 2) The ratio of positive reaction was 30.4% in epithelial hyperplasia of fibrocystic disease, 26.5% in fibroadenoma. 49.5% in intraductal carcinoma 71.6% in infiltrating ductal carcinoma, 85.2% in metastatic infiltrating ductal carcinoma, and 89.7% in relatively preserved neighboring lobules of infiltrating ductal carcinoma. In conclusion, the ras oncogene products are found by a significantly higher ratio in the more aggressive lesions, and the infiltrating ductal carcinoma might represent its potential of malignant transformation. 3) The expression of ras oncogene was heterogeneous in primary as well as metastatic mammary carcinomas.

Congenital Melanocytic Schwannoma in Ankle Joint Potentially Malignant: A case report.: Jong Tae Park, Chang Soo Park, Sang Woo Juhng, Kyu Hyuk Cho; Korean J Pathol. 1987;21(4):308-316.

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Abstract PDF: Congenital malignant melanocytic schwannoma in ankle joint was not reported on literature and it was a very interesting case. Light microscopically, melaninladen cells were mixed in abundant wavy spindle cells, some mitotic cells were also observed. Ultrastructurally, melanosomes in variable stages of development were scattered in the cytoplasm which had basal lamina. Collagen bundles were abundant in the intercellular connective tissue. It was histologically malignant tumor and clinically recurred. But in non-congenital potentially malignant melanocytic schwannoma which had been reported, reccurrence or distant metastasis were not noted. So, further clinical survey may be necessary for evaluation of the malignant behavior of this neoplasm.

Diffuse Neonatal Hemangiomatosis with Association of Massive Osteolysis and Arteriovenous Fistulae: An autopsy case.: Soon Pal Suh, Jong Tae Park, Wan Lee, Young Youn Choi, Chang Soo Park; Korean J Pathol. 1987;21(4):291-297.

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Abstract PDF: Diffuse neonatal hemangiomatosis is an uncommon disease that is characteristed by a diffuse nature of the lesions, and distinguished form a single or few, or superficial or deep, capillary, cavernous, or mixed hemangiomas occuring in early or adult life. We report an autopsy case of multiple hemangiomatosis, which is associated with massive osteolysis of right humerus and arteriovenous fistulae in surrounding soft tissues. The patient is a 23 day old female infant and had a 2.0x1.5 cm sized cystic destructive bony lesion which was located in the proximal shaft of right humerus. Right arm was hypertrophied, compared to the normal looking left. There were multiple hemangiomas in right humerus, lung, cutaneous skeletal muscles and nerves. This case shares clinical characteristics of Gorham's disease.

The Expression of ras and myc Oncogene in Transitional Cell Carcinoma of the Urinary Bladder.: Chang Soo Park, Byoung Dong Juhng, Sang Woo Juhng, Kyu Hyuk Cho; Korean J Pathol. 1987;21(4):233-239.

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Abstract PDF: The oncogenes, which have been detected in various human solid tumors, transform culture cells, and the level of m-RNA specific for an oncogene increases in the cellular extract of the tumor cells. These findings suggested that oncogene expression was closely related with carcinogenesis. Recently, oncogen products were considered as tumor markers, but it was not confirmed that the relationship between quantitative change of oncogene product and malignant potential of a neoplasm. To evaluate the relationship between the quantitative change of oncogene product and malignant potential, immunohistochemical staining for the ras and myc oncogene products was performed in the sections of papilloma and transitional cell carcinoma of urinary bladder. 1) Positive reaction of c-ras oncogene product was noted along the cell membrane and in the cytoplasm, and c-myc oncogene product in the nucleus, and along the unclear membrane and cell membrane. 2) Tissue expression of c-ras oncogene was homogeneous and strong in the transitional cell carcinoma rather than in papilloma. 3) The ratio of the positive cells with c-ras oncogene product was 35.1% in the papilloma, 79.4% in the grade I, 81.9% in the grade II, 87.6%, in the grade III of transitional cell carcinoma of the urinary bladder. There was a tendency for the ratio to increase with the degree of histological grading. 4) By the immunoperoxidase staining of c-myc oncogene product, the number of the cells showing positive nuclear staining incrased with the tumor grading.

The Effect of Uremic Plasma on the Proliferative Activity of CFU-GM in in-vitro Culture of Mouse Bone Marrow.: Chang Soo Park, Joo Yong Yoo; Korean J Pathol. 1987;21(4):215-226.

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Abstract PDF: The increased susceptibility in patients of chronic renal failure to infection has been reported to be attributed to defects in granulocyte and lymphocyte function and proliferative activity of hematopoietic cells. The definite cause of the frequent infection in uremic patients, however, is still controversial. The effect of uremic plasma on the aspect of the hematopoietic cells has been scarcely been studied. In the present study, mouse bone marrow was cultured with uremic plasma, to evaluate the effect of uremic plasma on the proliferative activity and morphological features of CFU-GM. The results obtained were as follows. 1) The number of colonies in group co-cultured with uremic plasma was more reduced than that of normal plasma group. 2) There was no difference between the group cultured with predialytic uremic plasma and that of postdialytic plasma in number of colonies, macroclusters and microclusters. 3) The forms of colony were granulocytic and monocytic forms at 5 day of culture. Electron microscopically, granulocytes disclosed electron dense azurophilic granules and electrolucent specific granules in the cytoplasm, and monocyte showed numerous vesicles and vacuoles in the cytoplasm which had finger-like projections. 4) The molecular weight of inhibitory factor in the uremic plasma was supposed to be less than 50,000 daltons.

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