Journal of Pathology and Translational Medicine

Chang Hun Lee

24 Articles

Molecular Biological Characteristics of Differentiated Early Gastric Cancer on the Basis of Mucin Expression.: Nari Shin, Hye Yeon Kim, Woo Kyung Kim, Min Gyung Park, Kyung Bin Kim, Dong Hoon Shin, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Gi Young Huh, Mee Young Sol, Do Youn Park; Korean J Pathol. 2011;45(1):69-78.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.69

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BACKGROUND
It is clear that the biologic characteristics of gastric cancer are different on the basis of mucin phenotypes. However, there are unabated controversies on the exact biologic differences of mucin expression in gastric cancer.
METHODS
We analyzed various protein expressions and microsatellite instability (MSI) status based on mucin expression in 130 differentiated early gastric adenocarcinoma cases. Furthermore, we evaluated the genomic alternation in 10 selected differentiated early gastric adenocarcinoma cases using array based comparative genomic hybridization (aCGH).
RESULTS
Intestinal mucin predominant subtype showed significantly elevated p53 protein and caudal-related homeobox 2 expression, and delocalization of beta catenin expressions compared to the gastric mucin predominant subtype. On MSI status, the gastric mucin predominant subtype more frequently showed unstable status than the intestinal mucin predominant subtype. CGH study showed more frequent chromosomal gain and loss in the intestinal mucin predominant subtype than the gastric mucin predominant subtype, albeit without statistical significance. Interestingly, there were significant differences in chromosomal alternation between four mucin phenotypes.
CONCLUSIONS
Study results suggest possible different points of biologic behaviors in early differentiated gastric adenocarcinomas by mucin expression type.

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Mucin Expression in Gastric Cancer: Reappraisal of Its Clinicopathologic and Prognostic Significance
Dae Hwan Kim, Nari Shin, Gwang Ha Kim, Geum Am Song, Tae-Yong Jeon, Dong-Heon Kim, Gregory Y. Lauwers, Do Youn Park
Archives of Pathology & Laboratory Medicine.2013; 137(8): 1047. CrossRef
Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes
Joo-Yeun Kim, Na Ri Shin, Ahrong Kim, Hyun-Jeong Lee, Won-young Park, Jee-Yeon Kim, Chang-Hun Lee, Gi-Young Huh, Do Youn Park
Korean Journal of Pathology.2013; 47(1): 28. CrossRef

Primary Myoepithelioma of the Testis: A Case Report.: Seong Muk Jeong, Jung Hee Lee, Won Young Park, Na Ri Shin, Woo Gyeong Kim, Gi Yeong Huh, Chang Hun Lee, Hong Koo Ha; Korean J Pathol. 2011;45:S20-S24.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S20

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Abstract PDF

Myoepitheliomas are well-established to occur in the salivary glands, but they have also been described in the breast, upper aerodigestive tract, skin, and soft tissues. We report here on a unique case of primary myoepithelioma that occurred in the right testis of a 28-year-old man. The tumor was entirely confined to the testis and it was clearly separated from the epididymis. Histopathology revealed mixed architectural patterns in which the reticular areas merged into the chondromyxoid stroma. The tumor cells, which were focally immunoreactive to pancytokeratin and S-100 protein, were round to ovoid and spindly arranged in cords, strands, and fascicles. They showed mild nuclear pleomorphism, sparse mitotic figures and a low Ki-67 proliferative index. There was no ductal differentiation in the tumor. To the best of our knowledge, there has been only one case report of a primary testicular myoepithelioma in the English medical literature.

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Primary cutaneous myoepithelial carcinoma: a case report and review of the literature
Markus Winther Frost, Torben Steiniche, Tine Engberg Damsgaard, Lars Bjørn Stolle
APMIS.2014; 122(5): 369. CrossRef
Imprint Cytology of Soft Tissue Myoepithelioma: A Case Study
Seok Ju Park, Ae Ri Kim, Mi Jin Gu, Joon Hyuk Choi, Duk Seop Shin
Korean Journal of Pathology.2013; 47(3): 299. CrossRef

Relationship between the Endogenous Hypoxic Markers Hypoxia Inducible Factor-1alpha, Carbonic Anhydrase IX, and Epithelial Mesenchymal Transition Regulator TWIST Expression in Non-small Cell Lung Cancer.: Jung Hee Lee, Won Young Park, Seong Muk Jeong, Min Ki Lee, Young Dae Kim, Dong Hoon Shin, Chang Hun Lee; Korean J Pathol. 2010;44(5):469-476.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.469

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Abstract PDF

BACKGROUND
The epithelial mesenchymal transition (EMT) is intimately associated with tumor hypoxia. The present study was conducted to investigate the immunohistochemical relationship between hypoxic and EMT-related molecules in non-small cell lung carcinoma (NSCLC).
METHODS
Immunohistochemical staining for hypoxia inducible factor (HIF)-1alpha, carbonic anhydrase (CA) IX, TWIST, and E-cadherin proteins was performed in 146 cases of NSCLC (80 cases of adenocarcinoma and 66 cases of squamous cell carcinoma) using tissue microarray blocks.
RESULTS
HIF-1alpha, TWIST, CA IX, and E-cadherin were expressed in 58 (40%), 90 (62%), 82 (56%), and 36 (25%) of 146 NSCLC cases, respectively. TWIST expression was positively correlated with HIF-1alpha expression (p = 0.03) and inversely correlated with E-cadherin expression (p < 0.01). TWIST and CA IX expression were not significantly interrelated, but each showed a relationship with histological tumor grade. However, the expression of these molecules had no significant effect on clinical staging or patient survival.
CONCLUSIONS
Although TWIST expression was correlated positively with HIF-1alpha expression and inversely correlated with E-cadherin, HIF-1alpha expression was not associated with E-cadherin expression. However, considering the relationship between HIF-1alpha and TWIST expression, further studies should be performed to demonstrate the role of hypoxia-induced EMT in NSCLC.

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Transcriptome analysis in gill reveals the adaptive mechanism of domesticated common carp to the high temperature in shallow rice paddies
Xiangbing Cheng, Fangcheng Li, Junjie Lu, Yuanlin Wen, Zhili Li, Jiayi Liao, Jiangwei Cao, Xumeng He, Jiamin Sun, Qigen Liu
Aquaculture.2024; 578: 740107. CrossRef
Clinicopathological and prognostic significance of Twist overexpression in NSCLC
Meng Li, Xing Zhang, Xiaoqing Xu, Jiubin Wu, Kaiwen Hu, Xiuwei Guo, Peitong Zhang
Oncotarget.2018; 9(18): 14642. CrossRef
The Role of TWIST in Ovarian Epithelial Cancers
Kyungbin Kim, Eun Young Park, Man Soo Yoon, Dong Soo Suh, Ki Hyung Kim, Jeong Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Kyung Un Choi
Korean Journal of Pathology.2014; 48(4): 283. CrossRef

The Interobserver Variability for Diagnosing Pulmonary Carcinoid Tumor.: Chang Hun Lee, Hee Kyung Chang, Hyoun Wook Lee, Dong Hoon Shin, Mee Sook Roh; Korean J Pathol. 2010;44(3):267-271.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.267

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Abstract PDF

BACKGROUND
Although the grade of pulmonary carcinoid tumor is routinely reported in pathology practice, there is a paucity of data on the level of agreement between pathologists.
METHODS
Data for 30 cases of surgically resected pulmonary tumors diagnosed as carcinoid tumors (19 typical carcinoids [TCs] and 11 atypical carcinoids [ACs]) were retrieved from four university hospitals. These cases were independently evaluated by five pathologists and were classified according to the 2004 World Health Organization (WHO) classification. Agreement was regarded as "unanimous" if all five pathologists agreed, and as a "majority" if four agreed. The kappa statistic was calculated to measure the degree of agreement between pathologists.
RESULTS
Unanimous agreement was achieved for 50.0% and a majority agreement for 83.3% of the 30 cases. The range of the kappa values extended from 0.37 to 0.89. After a consensus meeting, there was disagreement between the original diagnosis by each institute and the consensus diagnosis by the five pathologists for 40.0% of the 30 cases. Based on the consensus diagnosis, the agreement was greater for TCs than that for ACs.
CONCLUSIONS
Discriminating carcinoid tumors is subject to interobserver variability. This study indicates that there is a need for more careful standardization and application of diagnostic criteria for making the diagnosis of pulmonary carcinoid tumor.

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Limited additive value of the Ki‐67 proliferative index on patient survival in World Health Organization‐classified pulmonary carcinoids
Dorian R A Swarts, Martina Rudelius, Sandra M H Claessen, Jack P Cleutjens, Stefan Seidl, Marco Volante, Frans C S Ramaekers, Ernst J M Speel
Histopathology.2017; 70(3): 412. CrossRef
Interobserver Variability for the WHO Classification of Pulmonary Carcinoids
Dorian R.A. Swarts, Robert-Jan van Suylen, Michael A. den Bakker, Matthijs F.M. van Oosterhout, Frederik B.J.M. Thunnissen, Marco Volante, Anne-Marie C. Dingemans, Marc R.M. Scheltinga, Gerben P. Bootsma, Harry M.M. Pouwels, Ben E.E.M. van den Borne, Fran
American Journal of Surgical Pathology.2014; 38(10): 1429. CrossRef
Lung parenchymal invasion in pulmonary carcinoid tumor: An important histologic feature suggesting the diagnosis of atypical carcinoid and poor prognosis
Sang Yun Ha, Jae Jun Lee, Junhun Cho, Jiyeon Hyeon, Joungho Han, Hong Kwan Kim
Lung Cancer.2013; 80(2): 146. CrossRef
CD44 and OTP Are Strong Prognostic Markers for Pulmonary Carcinoids
Dorian R.A. Swarts, Mieke E.R. Henfling, Leander Van Neste, Robert-Jan van Suylen, Anne-Marie C. Dingemans, Winand N.M. Dinjens, Annick Haesevoets, Martina Rudelius, Erik Thunnissen, Marco Volante, Wim Van Criekinge, Manon van Engeland, Frans C.S. Ramaeke
Clinical Cancer Research.2013; 19(8): 2197. CrossRef
Altered expression of microRNA miR‐21, miR‐155, and let‐7a and their roles in pulmonary neuroendocrine tumors
Hyoun Wook Lee, Eun Hee Lee, Seung Yeon Ha, Chang Hun Lee, Hee Kyung Chang, Sunhee Chang, Kun Young Kwon, Il Seon Hwang, Mee Sook Roh, Jeong Wook Seo
Pathology International.2012; 62(9): 583. CrossRef
Differential expression of forkhead box M1 and its downstream cyclin‐dependent kinase inhibitors p27kip1 and p21waf1/cip1 in the diagnosis of pulmonary neuroendocrine tumours
Seung Yeon Ha, Chang Hun Lee, Hee Kyung Chang, Sunhee Chang, Kun Young Kwon, Eun Hee Lee, Mee Sook Roh, Boram Seo
Histopathology.2012; 60(5): 731. CrossRef

Expression of p63 and its Isoform, deltaNp63, in Non-Small Cell Lung Carcinoma.: Ick Doo Kim, Dong Hoon Shin, Kyung Un Choi, Do Youn Park, Gi Yeong Huh, Mee Young Sol, Min Ki Lee, Young Dae Kim, Chang Hun Lee; Korean J Pathol. 2009;43(4):321-328.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.321

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Abstract PDF: BACKGROUND
Several studies have been conducted on the role of the p63 gene family in non-small cell lung carcinoma (NSCLC). Nevertheless, the role of these genes in the development and progression of NSCLC remains controversial. This study was designed to examine the expression and clinicopathologic significance of the p63 family in NSCLC.
METHODS
Immunohistochemical staining was performed on 92 cases of NSCLC (47 squamous cell carcinomas [SqCCs] and 45 adenocarcinomas [ACs]) using tissue microarray blocks. The results were analyzed and correlated with clinicopathologic data. RESULTS: The expression of delta Np63 (Delta Np63) was elevated in SqCC (39/47), but not in AC (2/45; p<0.01). Both p63 and Delta Np63 had high expression in 39 SqCCs; p63 and Delta Np63 also had a similar geomorphologic distribution in most positive tumors. The expression of Delta Np63 was correlated with histologic type, gender, pT stage, p53 expression, and p63 expression. pT and pN stages were independent factors in survival (p<0.05, respectively).
CONCLUSIONS
The major p63 isoform in NSCLC, Delta Np63, had a strong correlation with p53 and p63, and was exclusively expressed in SqCC. However, our findings suggest that Delta Np63 was not an independent prognostic factor for NSCLC.

Assessment of Apoptosis by M30 Immunoreactivity and the Relationship with the MSI status and the Clinicopathological Characteristics of Colorectal Carcinomas.: Hyun Jeong Kang, Mee Young Sol, Do Youn Park, Soo Han Lee, Dong Hun Shin, Jee Yeon Kim, Kyung Un Choi, Hwal Woong Kim, Chang Hun Lee, Gi Young Huh; Korean J Pathol. 2006;40(5):319-325.

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Abstract PDF: BACKGROUND
The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 that's produced during the process of apoptosis, and it is reactive in formalin-fixed, paraffin-embedded tissue. The detailed nature of apoptosis in colorectal cancer is unclear, especially in regard to the MSI status and the clinicopathologic factors. The purpose of this study was to elucidate the apoptosis assessed by M30 immunoreactivity in colorectal cancer and its relationship with the MSI status and the various clinicopathologic factors of colorectal cancers.
METHODS
101 colorectal cancers were classified according to levels of MSI as 12 MSI-H, 4 MSI-L and 85 MSS. Apoptosis was quantified by immunohistochemistry with using M30 CytoDEATH anti-body.
RESULTS
The apoptotic index assessed by M30 was significantly increased in the MSI-H and MSI-L colorectal cancer compared to that in the MSS colorectal cancer. Right sided colon cancer showed a significant higher apoptotic index than did the left sided colon cancer. There was also a tendency for decreased apoptosis in metastatic colorectal cancers (Duke's stage D). There was somewhat of an increase of apoptosis in colorectal cancers with mucinous carcinoma and medullary carcinoma, and also in the colorectal cancers with an increased TIL count, but this was not statistically significant.
CONCLUSION
M30 immunoreactivity is a valuable method to detect apoptosis in formalin-fixed, paraffin-embedded tissue and it might explain that MSI-H colorectal cancer shows better clinical behavior than MSS colorectal cancer in regard to the increased apoptosis.

Significance of Galectin-3 Expression in Pulmonary Non-Small Cell Carcinoma.: Dong Hoon Shin, Chang Hun Lee, Hyun Jung Kang, Mee Young Sol, Min Ki Lee; Korean J Pathol. 2006;40(5):326-332.

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Abstract PDF: BACKGROUND
Non-small cell carcinoma (NSCC) has become the leading cause of cancer related death around the world. However, its prognostic factors remain poorly defined. Galectin-3 is an apoptosis related protein and its relationship with various cancers is presently the subject of research. This study was performed to investigate galectin-3 expression in NSCC and its value as a prognostic factor. METHODS: We examined the expression of galectin-3 and bcl-2 in surgically resected, lung NSCC, including 61 squamous cell carcinomas and 41 adenocarcinomas. PCNA staining was also performed. RESULTS: Each type of carcinoma showed cytoplasmic positivity in 18 (30.0%) and 25 (61.0%) cases, respectively. Squamous cell carcinoma showed increased galectin-3 expression in better differentiated tumors, whereas adenocarcinoma didn't show any relationship with the degree of differentiation. The cytoplasmic positivity of galectin-3 in both types of carcinoma was associated with poor prognosis. Bcl-2 expression didn't show any significant relationship with overall survival. Galectin-3 and bcl-2 expressions were positively correlated. However, co-expression of both proteins was not related to prognosis. CONCLUSIONS: These results indicate that galectin-3 expression in NSCC warrants attention as a possible prognostic factor.

Alteration of G1/S Cell Cycle Regulatory Proteins in Ovarian Epithelial Tumors.: Jee Yeon Kim, Hwal Woong Kim, Kyung Un Choi, Chang Hun Lee, Mee Young Sol, Hyun Jeong Kang, Dong Hoon Shin; Korean J Pathol. 2006;40(4):274-281.

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Abstract PDF: BACKGROUND
Disturbances of the cell cycle regulatory proteins are key events underlying the development and/or progression of human malignancies. The aim of this study was to evaluate the expression of G1/S cell cycle regulatory proteins in ovarian epithelial tumor.
METHODS
We simultaneously evaluated the expression of cyclin D1, cyclin E, CDK4, CDK2, p16, Rb, E2F1, p53 and the Ki67 labelling index (LI) by immunohistochemical methods in 148 cases of ovarian epithelial tumor of the benign (n=47), borderline (n=29), and malignant type (n=72).
RESULTS
The expression of cyclin E, CDK2, p16, Rb, E2F1, p53 and the Ki67 LI gradually increased from the benign type, through the borderline type, to the malignant tumors. Between the borderline and malignant tumors, the increased expression of cyclin E, E2F1, and p53, and the decreased expression of Rb were significantly associated with malignancy. The reduced Rb expression and the increased E2F1 expression were correlated with the FIGO stage and the histologic grade in the malignant ovarian epithelial tumors. CONCLUSIONS: Cyclin E, E2F1, and p53 overexpressions and the loss of Rb are the important components during carcinogenesis of ovarian epithelial tumors. Our results suggest that in- creased expression of E2F1 should be considered as a new parameter for the prognosis of patients with malignant ovarian epithelial tumors.

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.

Differential Expression of CD34 and Smooth Muscle Actin in the Stroma of Small Lung Adenocarcinoma with Mixed Bronchioloalveolar and Invasive Components.: Mee Sook Roh, Jong Woo Choi, Hyoun Wook Lee, Hyuk Chan Kwon, Tae Ho Park, Phil Jo Choi, Chang Hun Lee, Bong Kwon Cheon; Korean J Pathol. 2005;39(3):158-163.

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Abstract PDF: BACKGROUND
Absence of CD34-positive fibroblasts was reported within the stroma associated with invasive carcinomas. Conversely, tumor-associated desmoplastic stroma is characterized by the presence of smooth muscle actin (SMA)-reactive myofibroblasts. The present study was undertaken in order to elucidate whether the different distributions of stromal CD34-positive fibroblasts and SMA-reactive myofibroblasts are sensitive or specific markers of tumor invasion in small lung adenocarcinomas.
METHODS
Immunohistochemical stainings for CD34 and SMA were done in 37 peripheral adenocarcinomas less than 3.0 cm in diameter, including 16 adenocarcinomas with bronchioloalveolar carcinoma (BAC) and invasive components (mixed), and 21 invasive adenocarcinomas without BAC components (invasive).
RESULTS
The fibroblasts within the BAC components of the mixed group were mainly CD34-positive (81.2%) and preferentially SMA-negative (56.3%). In contrast, the fibroblasts within the invasive components of the mixed group were mainly CD34-negative (75.0%) and SMApositive (87.5%). The stromal cells of the invasive group were mostly negative for CD34 (90.5%) and positive for SMA (95.3%).
CONCLUSIONS
The loss of CD34 and the acquisition of SMA in the stromal cells within the tumor were related to tumor invasion (p<0.05). Thus, expression patterns of CD34 and SMA can be used to detect small foci of early stromal invasion in adenocarcinomas of the lung.

Obstructive Mucocele of the Appendix Secondary to Endometriosis: A Case Report.: Chang Hun Lee, Dong Hoon Shin, Jun Woo Lee; Korean J Pathol. 2004;38(6):419-422.

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Abstract PDF: Appendiceal mucoceles are usually associated with hyperplastic or neoplastic mucosal proliferation and obstructive lesions such as postinflammatory scarring, fecalith, carcinoid tumor, and endometriosis. Among these, an association with endometriosis is known to be very exceptional. We herein report on a rare case of obstructive mucocele of the appendix that was secondary to endometriosis in a 42-year-old patient with pelvic endometriosis. A computed tomography scan demonstrated a periappendiceal abscess-like lesion with a left adnexal mass that was suggestive of endometriosis. On gross examination, the periappendiceal lesion consisted of a mucin-filled cavity (the so-called mucocele) that was 1.8 cm in diameter, and it protruded into the cecal lumen. Microscopically, the lining epithelium of the cavity was almost totally denuded. A small amount of mucus spilled over outside the mucocele, but pseudomyxoma peritonei was not present. The wall of the mucocele showed the characteristic multiple foci of endometriosis involving predominantly the muscularis propria and the serosa of the appendix and adjacent cecal walls.

Clinicopathologic Significance of CD44s, CD44v5 and CD44v6 Expression in Non Small Cell Lung Carcinomas.: Jae Kyun Kim, Chang Hun Lee, Kyeong Min Lee, Jin Mi Song; Korean J Pathol. 2004;38(2):93-99.

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Abstract PDF: BACKGROUND
CD44 is a polymorphic family of transmembrane glycoproteins generated by alternative splicing of messenger RNA and is involved in the mechanism of tumor invasion and metastasis.
METHODS
The expression of selected CD44 molecules (CD44s, CD44v5, and CD44v6) was determined immunohistochemically in 84 cases of non small cell lung carcinomas (NSCLCs). The results were compared with PCNA index, microvessel density (MVD), and clinicopathological parameters including patient? survival.
RESULTS
CD44s showed a positive reaction in 61.9% (52/84) of NSCLCs, CD44v5 in 73.8% (62/84), and CD44v6 in 39.3% (33/84). Squamous cell carcinomas (SCCs) displayed preferential expression of all CD44 molecules in comparison with adenocarcinomas (ACs) (p<0.001). As a whole, the expression of CD44 molecules was not correlated with clinical parameters (stage, TNM-T, and TNM-N), PCNA index, or MVD. For ACs only, however, CD44v5 expression was negatively correlated with PCNA index (p<0.05). Poor survival was correlated with CD44v5 expression in ACs and CD44v6 in SCCs (both, p<0.05).
CONCLUSIONS
These findings suggest that CD44 molecule in NSCLC could be a distinctive phenotypic marker for SCC, and the possibility that CD44v5 and CD44v6 are in some way instrumental in conditioning the biologic behavior of NSCLC according to major histologic types.

Expression of Hypoxia-inducible Factor-1 alpha Protein in Stages I and II Squamous Cell Carcinomas of the Uterine Cervix: Relationship with p53 Protein and VEGF Expressions.: Dong Soo Suh, Chang Hun Lee, Kang Suek Suh, Man Soo Yoon; Korean J Pathol. 2003;37(2):79-86.

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Abstract PDF: BACKGROUND
Under hypoxia, hypoxia-inducible factor-1alpha (HIF-1alpha) is known to activate the expression of various genes, including angiogenesis-related genes. The aim of this study was to evaluate the expression of HIF-1alpha protein and its relationship with p53 protein expression and angiogenesis in the squamous cell carcinoma (SCC) of the uterine cervix.
METHODS
Using immunohistochemical methods, the expression of HIF-1alpha protein, p53 protein, vascular endothelial growth factor (VEGF), and microvessel count were evaluated in seventy cases of FIGO stages I and II SCC; and their results were compared with age, stage, and pelvic lymph node metastasis.
RESULTS
Positive nuclear staining for HIF-1alpha protein was noted in 19 cases (27.1%). Carcinoma in situ or dysplastic lesions also revealed positive nuclear reaction along the lower part of the epithelium. The expression of HIF-1alpha protein was significantly related with those of p53 protein and VEGF (p<0.05), but not with other clinicopathologic parameters. The microvessel count showed a significant difference regarding stage and VEGF expression (pand<0.05).
CONCLUSION
These findings suggest that HIF-1alpha expression in SCCs of the uterine cervix might be the early event of carcinogenesis and could be associated with p53 protein and VEGF expression. However, the prognostic significance of HIF-1alpha expression in stages I and II SCCs is undetermined.

Fine Needle Aspiration Cytology of Insular Carcinoma of the Thyroid.: Kyung Un Choi, Jee Yeon Kim, Jin Sook Lee, Chang Hun Lee; Korean J Cytopathol. 2003;14(1):17-21.

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Abstract PDF: Insular carcinoma of the thyroid(ICT) is an uncommon thyroglobulin-producing neoplasm, intermediate between well differentiated and anaplastic carcinoma. Only a few publications have addressed the fine needle aspiration cytologic(FNAC) findings from ICT. We experienced a case histologically diagnosed as ICT and with preoperative FNAC in a 52-year-old woman. The FNAC displayed scanty colloid and abundant monomorphic follicular cells presented singly, in small loose aggregates, and in cohesive trabecular or acinar clusters. Intact insulae of tumor cells were also identified. Necrosis and mitosis were rare. Tumor cells showed round and monomorphic nuclei, finely granular chromatin, and inconspicuous nucleoli. When insular structure is identified in thyroid FNAC specimen, ICT should be included in the differential diagnosis. Herein we discuss and review the cytologic criteria for separation of ICT from other thyroid neoplasms.

Expression of Fas/Fas Ligand and Its Relationship with Apoptosis in Chemically Induced Preneoplastic Lesions in Rat Liver.: Hye Jin Lee, Do Youn Park, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Mee Young Sol, Kang Suek Suh; Korean J Pathol. 2001;35(5):383-390.

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Abstract PDF: BACKGROUND
Apoptosis of hepatocytes plays a major role in experimental hepatocarcinogenesis of rats. But sequential change and localization of Fas and Fas ligand (FasL) in preneoplastic lesions and the relationship with apoptosis are not clearly elucidated.
METHODS
We investigated sequential change and localization of Fas/FasL and its relationship to apoptosis in preneoplastic lesions of chemical hepatocarcinogenesis in rats using northern blot analysis, immunohistochemistry and terminal deoxynucleotidyl transferase end labeling (TUNEL) assay.
RESULTS
We found that mRNA of Fas and Fas ligand increased for up to 42 days and 14 days after partial hepatectomy, respectively, and thereafter decreased with time. Fas protein was localized on the cytoplasm of hepatocytes of preneoplastic lesions, as well as on the cytoplasmic membrane of the adjacent liver parenchyme. Fas negative preneoplastic lesions were evident at 42 days after partial hepatectomy. FasL protein was found only in the cytoplasm of hepatocytes of preneoplastic lesions, instead of in the adjacent liver parenchyme. FasL-positive hepatocytes increased with time for up to 14 days after partial hepatectomy and therafter decreased. Also, TUNEL-positive apoptotic cells increased with time and were more numerous in the adjacent liver parenchyme than in the preneoplastic lesions.
CONCLUSIONS
It was suggested that Fas/FasL-mediated apoptosis might be one of the major mechanisms for controlling apoptotic cell death in the promotion stage of chemical hepatocarcinogenesis.

Primary Extragastrointestinal Stromal Tumor (EGIST) of the Greater Omentum.: Kyung Un Choi, Jee Yeun Kim, Do Youn Park, Chang Hun Lee, Mee Young Sol, Kang Suek Suh, Jun Woo Lee; Korean J Pathol. 2001;35(4):347-350.

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Abstract PDF: Gastrointestinal stromal tumors (GISTs) were recently defined as spindle cell, epithelioid, or occasionally, pleomorphic mesenchymal tumors of the gastrointestinal tract that express the CD117 (proto-oncogene c-kit protein, stem cell factor receptor), as detected using immunohistochemistry. And they show a new tendency to include the CD117-positive mesenchymal spindle cell or epithelioid neoplasms primary in the omentum and mesentery, and is so termed extragastrointestinal stromal tumors (EGISTs). Omental EGISTs are very rare and similar to their gastrointestinal counterpart. We present a case of primary EGIST of the greater omentum in a 58-year-old man. The resected tumor mass measured 20X15X5 cm and weighed 1,150 g. The cut surface displayed a central cystic change and partial mural nodules. Microscopically, most parts of the tumor were composed of round or polygonal cells, with many of them containing perinuclear vacuoles. The mitotic count was less than one per 50 high-power-fields. Immunohistochemically, the tumor cells were diffusely positive for CD117 and vimentin, and focally for smooth muscle actin and CD34. Ultrastructurally, partially smooth muscle differentiation was confirmed in this case.

Expression of Met Protein in Colorectal Carcinoma.: Kyung Un Choi, Jin Sook Lee, Chang Hun Lee, Mee Young Sol, Kang Suk Suh; Korean J Pathol. 2000;34(7):501-508.

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Abstract PDF: Met protein is a transmembrane 190 kD heterodimer with tyrosine kinase activity, encoded by c-Met oncogene. It serves as a high affinity receptor for hepatocyte growth factor (HGF)/scatter factor (SF), a cytokine which stimulates cell proliferation, motility, and invasion. In this study, we immunohistochemically evaluated the expression of Met/hepatocyte growth factor receptor in colorectal cancers. Met protein was expressed in 31 of 72 patients (43.1%). The staining pattern was cytoplasmic in nature, present throughout the tumor, and showed variable intensity from case to case. The relationship between the expression rate and intensity, and age and sex of patients, tumor size (p=0.645), tumor site (p=0.902) and tumor differentiation (p=0.844) was not statistically significant. The expression rate and intensity were significantly correlated with lymphovascular invasion (p=0.001), lymph node metastasis (p=0.010), depth of invasion (0.019), and stage (p=0.023). Cytoplasmic accumulation of Met protein was not associated with enhanced PCNA index of tumor cells (p=0.052). These results suggest that Met protein may play an important role in the invasion and metastasis of colorectal cancer cells.

Expression of p53 and MDM2 Proteins in Thyroid Carcinomas.: Chang Hun Lee; Korean J Pathol. 1998;32(4):255-260.

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Abstract PDF: The nuclear protein p53 is a tumor suppressor gene product that functions in pathways of cell cycle control and in the repair of damaged DNA. The MDM2 gene codes for a cellular protein that can complex the p53 gene product and negatively regulate its function. Interestingly an autoregulatory feedback loop is set up to regulate the activity of p53 protein and MDM2 gene expression. To evaluate the role of p53 and MDM2 proteins in thyroid carcinogenesis, the author tried immunohistochemical studies in the paraffin embedded sections of 58 thyroid carcinoma cases, including 30 papillary carcinomas, 20 follicular carcinomas, and 8 undifferentiated carcinomas. p53 protein expression was found in 8 cases (26.7%) of papillary carcinomas. It was found in all the cases of undifferentiated carcinomas and not found in the follicular carcinomas. The staining intensity and the frequency scores were more prominent in undifferentiated carcinomas. MDM2 protein expression was found in only 6 cases of papillary carcinomas. It was not expressed in follicular carcinomas or undifferentiated carcinomas. The staining intensity is less than moderate and the frequency score was usually focal. In papillary carcinomas, the correlation of p53 and MDM2 expression was insignificant. In conclusion, p53 may play a major role in tumorigenesis or the progression of undifferentiated carcinomas, but not in the other carcinomas. As compared with papillary carcinomas, follicular carcinomas are regarded as taking a different carcinogenetic pathway. The overexpression of p53 and MDM2 proteins in papillary carcinomas is presumed not to be necessarily correlated with the p53-MDM2 complex formation.

Primary MALT(mucosa-associated lymphoid tissue) Type Lymphoma of the Liver.: Do Youn Park, Jee Yeon Kim, Hyo Jeong Chae, Jin Sook Lee, Chang Hun Lee, Mee Young Sol, Kang Suek Suh, Sun Kyung Lee; Korean J Pathol. 1997;31(12):1317-1319.

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Abstract PDF: Primary non-Hodgkin' lymphomas of the liver, an organ normally devoid of a native lymphoid tissue, are very rare. We recently experienced a case of a primary low-grade hepatic B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type in a 36-year-old woman. The ultrasonography revealed a 5 cm sized mass in the right lobe of the liver. A right segmentectomy of the liver was done and showed a relatively well-circumscribed brownish yellow lobulated homogenous mass, measuring 5.5x4.5 cm in size. Histologic sections of liver mass revealed large lymphoid follicles with reactive germinal centers, follicular colonization by centrocyte-like cells (CCL cells), and lymphoepithelial lesions. The CCL cells were positive for B-cell (CD20), LCA (CD45RA), Bcl-2 oncoprotein, and lambda light chain.

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

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

Cytologic Features and Distribution of Primary Sites of Malignant Cells in Body Cavity Fluids .: Kang Suek Suh, Chang Hun Lee, Hyun Ok Kim; Korean J Cytopathol. 1997;8(1):35-46.

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Abstract PDF: The authors reviewed 167 malignant effusions from 110 patients, of which the primary site was established on the basis of either biopsy or surgical resection of the primary neoplasm. Main factors analysed were the distribution of primary organs and the cytohistologic correlation of body cavity effusions. The 167 fluid specimens from 110 patients consisted of 90 cases(53.9%) of pleural, 68(40.7%) of peritoneal, and 9(5.4%) of pericardial origins. Histologically they consisted of 82 cases(74.5%) of adenocarcinoma, 8(7.3%) of malignant lymphoma, 6(5.5%) of squamous cell carcinoma, and 3(2.7%) of small cell carcinoma. The most common site among the primary lesions was the stomach in 25 cases(22.7%) followed by the lung in 21 (19.1%), ovary in 17(15.5%), and breast in 7(6.4%). As for the distribution of primary tumors in adenocarcinoma, the most common site was lung in 16 cases (48.5%) in pleural fluid and stomach in 22(48.9%) in peritoneal fluid. In pericardial effusions, all 5 cases were from the lung. As a whole, the cytologic findings of malignant effusion were fairly representative of histologic characteristics of primary lesions. Thus, when the primary lesion is unknown, careful evaluation of effusion cytology is presumed to be a helpful tool for tracing the primary tumor.

Metastatic Renal Cell Carcinoma in Maxillary Sinus: A case report.: Gyeong Yeob Gong, Chang Hun Lee, Kang Suek Suh, Sun Kyung Lee; Korean J Pathol. 1991;25(4):392-394.

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Abstract PDF: Metastases to the sinonasal tract are infrequent occurrences from primaries below the clavicles. The total number of reported cases to date is less than 100. There is, however, complete unanimity concerning the histologic type of metastatic neoplasm most often encountered. An interesting phenomenon, generally attributable only to breast and renal cell carcinoma, is the late recurrence of the malignant tumor, even 10 or more years after operation. A 61 year-old-male was admitted to ENT due to frequent epistaxis and right facial swelling. CT scan revealed a huge soft tissue density mass I right maxillary sinus with extension into nasopharynx and deviation of nasal septum. The histologic diagnosis was metastatic renal cell carcinoma. He had left nephrectomy because of renal cell carcinoma, 14 years ago. We report a case of metastatic renal cell carcinoma of maxillary sinus in view of rarity, and a brief review of the literature related to this type of tumor is presented.

Grooved Nuclei in Thyroid Papillary Carcinoma.: Chang Hun Lee, Kang Suek Suh; Korean J Pathol. 1991;25(3):185-195.

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Abstract PDF: Recently nuclear grooving has been introduced to be a reliable diagnostic criterion for papillary thyroid carcinoma, in addition to known clear nuclei and intranuclear cytoplasmic inclusions. Now this study is undertaken to assess the diagnostic value of this new clue. The results obtained are as follows : 1) 35 follicullar carcinomas, 106 follicular adenomas and 56 adenomatous goiters were studied as control groups. Grooved nuclei were positive in 22.9% of follicular carcinomas, 19.8% of follicular adenomas and 5.4% of adenomatous goiters, whereas intranuclear cytoplasmic inclusions in 11.4%, 11.3% and 7.1% : and clear nuclei in 22.9%, 23.6% and 5.4%, respectively. 2) Among 105 papillary carcinomas the frequencies of grooved nuclei, intranuclear cytoplasmic inclusions and clear nuclei were 93.3%, 84.8% and 79.0%, respectively. Incidence difference between grooved nuclei and clear nuclei was significantly recognized(p<0.05). 3) Among variants of papillary carcinoma including mixed, pure, occult sclerosing and follicular types, the frequencies of grooved nuclei were 96.7%(59/61), 86.2%(25/29), 100%(13/13) and 50.0%(1/2), respectively. In comparison the frequency of the mixed types was mildly more increased than that of the pure(p<0.05). 4) Among 44 aspiration biopsy cytology cases, which were identified histologically as papillary carcinoma, the frequencies of grooved nuclei and intranuclear cytoplasmic inclusions were 65.9% and 70.5%, respectively. Therefore it is suggested that grooved nuclei be a valuable diagnostic feature of papillary thyroid carcinoma, along with other nuclear findings.

Merkel Cell Carcinoma: A case report associated with squamous cell carcinoma.: Chang Hun Lee, Gyeong Yeob Gong, Kang Suek Suh, Sun Kyung Lee; Korean J Pathol. 1991;25(2):164-171.

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Abstract PDF: Merkel cell carcinoma is a relatively uncommon, cutaneous, neuroendocrine neoplasm that was first recognized by Toker in 1972. Occasionally it is found concurrent with squamous cell carcinoma or basal cell carcinoma and in them cases, the coexistence of them is suggesive of presenting the effect of a common carcinogenic influence on two distinct precursor cells. Now the authors report a case of Merkel cell carcinoma associated with squamous cell carcinoma arising in the overlying epidermis, and a brief review of literatures is introduced. The patient was a 75-year-old female, who had noticed a reddish brown, ulcerated mass on the right buttock. It had progressively enlarged to become lemon-size during last 4 months. The right buttock mass excised measured 10x8x3 cm and was gray white, solid, with an ill-defined marigin. Histologically the tumor was located in the dermis and was lacking in connection with the epidermis in which invasive squamous cell carcinoma developed. The neoplastic cells were arranged in a diffuse, lymphoma-like pattern or trabecular arrangement and their cytologic details were reminiscent of small cell carcinoma of the lung, On electron microscopy the cells displayed many neurosecretory granules averaging about 100nm in diameter, intermediate filaments and desmosomes. Immunohistochemically a ball-like immunostaining for keratin, resembling an inclusion body, was seen, but other markers, including neuron-specific enolase, vimentin, S-100 protein and leukocyte common antigen, were unrewarded.

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