Journal of Pathology and Translational Medicine

Mee Yon Cho

28 Articles

CpG Island Methylation According to the Histologic Patterns of Early Gastric Adenocarcinoma.: Junjeong Choi, Mee Yon Cho, So Young Jung, Khalilullah Mia Jan, Hyun Soo Kim; Korean J Pathol. 2011;45(5):469-476.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.469

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BACKGROUND
Although the importance of aberrant DNA methylation in the development of gastric adenocarcinoma has been described, the mechanism of pathogenesis has not been revealed yet. We quantitatively analyzed methylation of four CpG islands and one repetitive DNA element, according to the histologic features of adenocarcinoma with precursor lesions.
METHODS
We divided the cases as adenocarcinoma with intestinal type precursors (type A, n=19 cases) and adenocarcinoma with diffuse type precursors (type B, n=19 cases). We micro-dissected tumor cells and matched non-neoplastic gastric mucosa from the hematoxylin and eosin-stained slides.
RESULTS
A total of 20 CpG sites of long interspersed nucleotide element-1 (LINE1), RAR-related orphan receptor alpha (RORA), Kruppel-like factor 7 (KLF7), mutL homolog 1 (MLH1), MINT25, and CD133 were analyzed. Methylation was determined by bisulfate-pyro-sequencing, and hypomethylation of LINE1 and CD133 was noted in the tumors, compared to the levels in the non-neoplastic gastric mucosa (p=0.014 and p=0.015, respectively). A statistically different methylation pattern of CpG sites at CD133 and KLF7 was noted only in type B lesions, compared to that in matched non-neoplastic gastric mucosa (p=0.027 and p=0.043, respectively).
CONCLUSIONS
Given that aberrant methylation occurs in a relatively early phase of carcinogenesis, different patterns of methylation may determine the carcinoma phenotype. However, further large-scale study is required to clarify the significance of this difference.

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Molecular function of Krüppel-like factor 7 in biology
Yi Mao, Yuechan Chen, Zhiwei Zhang
Acta Biochimica et Biophysica Sinica.2023; 55(5): 713. CrossRef
DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis
YOSEP CHONG, KHALILULLAH MIA-JAN, HOON RYU, JAMSHID ABDUL-GHAFAR, JIJGEE MUNKHDELGER, SAYAMAA LKHAGVADORJ, SO YOUNG JUNG, MIRA LEE, SUN-YOUNG JI, EUNHEE CHOI, MEE-YON CHO
Oncology Reports.2014; 31(6): 2535. CrossRef

Telomerase Activity in Urethane-Induced Mouse Lung Tumorigenesis.: Ji Sun Song, Soon Hee Jung, Sang Yeop Yi, Hwa Eun Oh, Mee Yon Cho, Kwang Hwa Park; Korean J Pathol. 2011;45(3):261-270.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.261

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Abstract PDF

BACKGROUND
Telomerase activity in precancerous conditions of lung adenocarcinomas has not been well studied. This study is designed to investigate the role of telomerase in premalignant lesions of urethane-induced mouse lung adenocarcinoma.
METHODS
We harvested A/J mouse lung tissues at 3, 6, 9, 12, 28, 41, and 48 weeks after intraperitoneal urethane treatment, and classified each lesion in terms of histologic findings. We examined telomerase activity using a modified version of the telomeric repeat amplification protocol assay using both gel-based and enzyme linked immunosorbent assay methods. An immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) was performed.
RESULTS
In urethane-induced mouse lung tissues, it was sequentially developed from hyperplasia, adenoma, and eventually to adenocarcinoma. Telomerase activity began to show a positive level in tissues with no histologically visible nodule after urethane administration. It revealed a statistically significant increase in hyperplasia compared to the "control" lung tissue (p<0.05), which was proportionally elevated relative to adenoma and adenocarcinoma. There was a direct correlation between telomerase activity and the PCNA labeling index (p<0.05).
CONCLUSIONS
The elevation of telomerase activity in normal-appearing lung lesions is thought to be a possible marker of early detection of pulmonary adenocarcinoma.

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Non-invasive quantification of cell-free DNA mutations in plasma during lung tumor progression in mice
Soo-Jin Kim, Eunhee Kim, Kyung-Taek Rim
Cancer Biomarkers.2017; 20(4): 477. CrossRef

First Report of a Gangliocytic Paraganglioma Arising in a Tailgut Cyst.: Yosep Chong, Mee Yon Cho; Korean J Pathol. 2010;44(4):435-440.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.435

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Abstract PDF

Here we present the first report of a gangliocytic paraganglioma arising in a tailgut cyst; it occurred in a 56-year-old man. Tailgut cysts are uncommon congenital hamartomatous lesions that arise in the retrorectal presacral space in infants or adults. Benign or malignant tumors associated with tailgut cysts are rarely described; the most common tumors are adenocarcinomas and carcinoid tumors. A gangliocytic paraganglioma is a rare benign tumor that occurs nearly exclusively in the second portion of the duodenum. Rare cases have been reported at other locations, but a tailgut cyst has never been described. In our case, a resected 3.9 x 3.3 x 3 cm mass was composed predominantly of a solid yellow white neuroendocrine tumor within the area of a tailgut cyst. The neuroendocrine component of this tumor was different from previously described carcinoid tumors with respect to the histologic findings of neural differentiation as well as the intermixed typical gangliocytic features highlighted by immunohistochemical stains for S-100 protein and neurofilament. Although an intermixed area of the tailgut cyst and gangliocytic paraganglioma were found in some areas, the pathogenesis of this tumor remains to be elucidated.

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Diagnosis of Tailgut Cyst in Gynecologic Patients: Systematic Review of the Literature
Polina Schwarzman, Salvatore Andrea Mastrolia, Yael Sciaky-Tamir, Joel Baron, Boaz Sheizaf, Giuseppe Trojano, Reli Hershkovitz
Journal of Endometriosis and Pelvic Pain Disorders.2017; 9(3): 168. CrossRef
Fine Needle Aspiration Cytology Diagnosis of Tailgut Cyst: A Rare Entity
Farhan Asif Siddiqui, Rajan Chopra, Yusef Al-Marzooq
Acta Cytologica.2014; 58(2): 217. CrossRef

Porposal for Creating a Guideline for Cancer Registration of the Gastrointestinal Tumors (I).: Mee Yon Cho, Yun Kyung Kang, Kyoung Mee Kim, Hee Kyung Chang, Hee Jin Chang, Mee Soo Chang, Joon Mee Kim, Dae Young Kang, Chanil Park, Jin Hee Sohn; Korean J Pathol. 2008;42(3):140-150.

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Abstract PDF: BACKGROUND
Cancer registries are fundamental for cancer control and multicenter collaborative research. However, there have been discrepancies among pathologists in classifying cancer and assigning the codes according to the International Classification of Disease Oncology 3 (ICD-O3). To improve the quality of cancer registries as well as to prevent the conflict with medical insurance compensation, a guideline for the coding of cancer is mandatory.
METHODS
AND RESULTS: Funded by the Management Center for Health Promotion, 40 members of the Gastrointestinal Pathology Study Group and the Cancer Registration Committee of the Korean Society of Pathologists participated in the 1st workshop for gastrointestinal tumor registration. The subjects of gastric epithelial tumor, intramucosal carcinoma of the colon, carcinoid tumor, gastrointestinal stromal tumor and appendiceal mucinous tumor were discussed to create a guideline. A survey to obtain consensus for the guideline proposed by the workshop was carried out by the members of the Korean Society of Pathologists and 240 members completed the questionnaire.
CONCLUSION
Although there are some issues to be discussed further, such as coding of high grade dysplasia/adenoma and intramucosal carcinoma of stomach and colon, the members agreed upon most parts of the proposed guideline. Therefore, we suggest using the ICD-O3 coding guideline for gastrointestinal tumor.

Genetic Analysis of Epstein-Barr Virus Latent Membrane Protein 1 and Immunohistochemical Expression of Transforming Growth Factor (TGF)-beta1, TGF-betaRII, p21, p16, E2F1, Thymidylate Synthase, and NF-kappaB in Epstein-Barr Virus Encoded RNA-positive Gastric Adenocarcinoma: Mee Yon Cho, Minseob Eom, Kwang Hwa Park, Mee Dong Kim, Seung Hoon Sung, Myoung Soo Kim, Dae Sung Kim, Sun Ju Choi; Korean J Pathol. 2006;40(3):176-184.

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Abstract PDF: BACKGROUND
:Although clinicopathologic differences have been described between Epstein-Barr virus (EBV)-positive and negative gastric adenocarcinomas, the pathogenetic basis for these differences remains unclear. In this study, efforts were made to confirm that expression of EBV-latent membrane protein (LMP1) and immunohistochemical characteristics of EBVpositive gastric adenocarcinomas.
METHODS
We investigated genomic deletion, and RNA & protein expression of the EBV-LMP1, as well as immunohistochemical protein expression of transforming growth factor (TGF)-beta1, TGF-bata RII, p21, p16, E2F1, thymidylate synthase, and NF-kappaB in relation to EBV positive gastric adenocarcinoma.
RESULTS
A total of 38 Epstein-Barr Virus Encoded RNA-positive and 80 negative gastric carcinomas were examined. A 30 bp DNA deletion in the EBV-LMP1 gene, initiating at codon 342, was detected in 94.4% of EBVpositive cases. By RT-PCR and western blotting, EBV-LMP1 mRNA and protein expressions were absent in all cases, re-gardless of DNA deletion. No significant differences in TGF-bata1, TGF-betaRII, p21, NF-kappaB, E2F1, or thymidylate synthase expression were identified. However, the decreased expression of p16 was found in 84.2% of EBV-positive carcinomas, relative to only 57.5% of EBV-negative tumors (p=0.024).
CONCLUSION
EBV-LMP1 DNA deletion, mRNA and protein losses are highly prevalent in EBV-positive gastric adenocarcinoma among Korean patients, along with decreased p16 expression.

A High Thymidylate Synthase Expression is Related to Better Outcome for Advanced Gastric Cancer Patients Treated with 5-FU Chemotherapy after Curative Resection.: Mee Yon Cho, Sang Yeop Yi, Min seob Eom, Shu Peng Zhang, Hwan Sik Kim, Jong In Lee, Dae Sung Kim; Korean J Pathol. 2006;40(2):128-136.

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Abstract PDF: BACKGROUND
The expressions of thymidylate synthase (TS), E2F-1, pRb, and p53 are correlated with DNA synthesis. The significance of their expressions is still controversial for predicting the outcome of 5-fluorouracil (5-FU) therapy in the patients with advanced gastric carcinoma. Furthermore, their prognostic value in the metastatic lesions of gastric carcinoma has not yet been confirmed.
METHODS
To ascertain their prognostic value, we immunohistochemically analyzed the expressions of TS, E2F-1, pRb, and p53 in the primary tumors and the related metastatic lymph nodes, and we then compared the survival between the high and low expression group of each protein. Ninety four patients with advanced gastric carcinoma who were treated by complete resection and adjuvant 5-FU chemotherapy were analyzed.
RESULTS
The TS expression in primary tumors was significantly correlated with that of E2F-1. The expression of these genes showed no significant difference between the primary tumors and the metastatic lymph nodes except for E2F-1, which was significantly higher in the lymph node metastasis than in the primary tumors. After complete resection and 5-FU-based adjuvant chemotherapy, patients with a high TS expression in the primary tumors showed a longer survival than those patients having primary tumors with a low TS expression (p=0.0392).
CONCLUSION
A high TS expression in the primary tumors may be related to a better outcome for advanced gastric cancer patients who were treated with 5-FU chemotherapy after curative resection.

Isolated Intracranial Rosai-Dorfman Disease: A Case Report.: Jin Kyu Park, Mee Yon Cho, Kwang Hwa Park, Jhin Soo Pyen; Korean J Pathol. 2004;38(6):430-433.

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Abstract PDF: Rosai-Dorfman disease (RDD) is an idiopathic histioproliferative disorder of the lymph nodes and extranodal sites. Central nervous system involvement is extremely rare. Intracranial RDD, especially the isolated form, resembles meninigioma both clinically and radiologically. Here, we report a case of isolated, intracranial, dura-based RDD. The patient presented with headache and dizziness with no evidence of lymphadenopathy. Histologically, the lesion consisted of large histiocytes with emperipolesis and lymphoplasma cell infiltrates with a fibrotic background. We discuss the differential diagnosis of this lesion. To our knowledge, this is the first reported Korean case of intracranial RDD.

Relationship between Epstein-Barr Virus (EBV), Apoptosis and Lymphocytic Infiltration in Gastric Carcinoma with Lymphoid Rich Stroma.: Tae Heon Kim, Mee Yon Cho, Sang Yeop Yi, Woo Hee Jung, Kwang Hwa Park; Korean J Pathol. 2001;35(5):368-375.

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Abstract PDF: BACKGROUND
Gastric carcinoma with lymphoid rich stroma (GCLRS) is an undifferentiated gastric carcinoma with heavy lymphocytic infiltrate. In order to clarify the relationship between lymphocytic infiltration and apoptosis in gastric carcinoma, we investigated the association of apoptosis with apoptotic proteins and Epstein-Barr Virus (EBV) expression in GCLRS.
METHODS
We performed immunohistochemical stains for bcl-2, bax and in situ hybridization for EBER (Epstein-Barr virus encoded RNA)-1 and the terminal deoxynucleaotidil transferase mediated dUTP-digoxigenin nick end labelling (TUNEL) technique using 47 out of 1635 gastric carcinoma cases.
RESULTS
The prevalence of GCLRS was 1.47% (24/1635). The prevalence of EBV involvement in GCLRS (79%, 19/24) was significantly higher than that of gastric carcinoma with lymphoid poor stroma (GCLPS) (8.7%, 2/23). The immunohistochemical stain for bcl-2 revealed negative expressions in all cases, but that of bax was positive for in all cases. bax was significantly correlated with the apototic index (P<0.05). There was no statistical significance between lymphocytic infiltration and apoptosis. The lymphocytic infiltration significantly correlated with the expression of EBV (P<0.05) but not with survival rate and apoptosis. However, most of the GCLRS displayed low clinical stages(stage IA, B), and we suggest that was a proper reason for a good prognosis.
CONCLUSIONS
These results support that EBV is associated with GCLRS, and there is no relationship between apoptosis and bcl-2, bax and prognosis. They also suggest that EBV infection play an important role in the gastric carcinogenesis.

Expression of Cyclin D1, Cyclin E, p21Cip1 and p27Kip1 in Chemically Induced Rat Mammary Tumor Treated with Tamoxifen and Transforming Growth Factor-1.: Tae Jung Jang, Jae Hum Park, Mee Yon Cho, Ki Kwon Kim, Jung Ran Kim; Korean J Pathol. 2001;35(2):151-157.

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Abstract PDF: BACKGROUND
Tamoxifen (TAM) inhibits the action of estrogen by binding to estrogen receptors, and also has non-estrogen receptor mediated cytostatic activities. Transforming growth factor-1 (TGF-1) inhibits the proliferation of many other cell types, such as epithelial, hematopoietic and endothelial cells.
METHODS
We investigated the effects of tamoxifen on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors and the expression of cyclin D1, cyclin E, p21Cip1, and p27Kip1 by performing immunohistochemistry and Western blot analysis, and studied whether TGF-1 injection amplified the effects of TAM. When tumor size reached between 10-15 mm in the largest dimension, the rats were divided into 3 groups: DMBA-control group (n=12), DMBA-TAM group (n=14) and DMBA-TAM plus TGF-1 group (n=5).
RESULTS
The consecutive administration of TAM markedly decreased the tumor development compared with the DMBA-control group. The DMBA-TAM and DMBA-TAM plus TGF-1 groups showed decreased expression of bromodexoyuridine, cyclin D1, cyclin E, and p21Cip1 when compared with those of the DMBA-control group. On the other hand, the labeling index of p27Kip1 was higher in the DMBA-TAM plus TGF-1 group than in the DMBA-control group.
CONCLUSION
TAM suppresses tumor development, which may be associated with down-expression of cyclin D1 and cyclin E, and overexpression of p27Kip1, and addition of TGF-1 does not influence tumor development treated by TAM.

Does the Colorectal Cancer Among Koreans Share the Same Pathological Features by Geographical Distribution: A Nationwide Survey of Surgically Resected 1,676 Cancers from 1,602 Patients.: Mee Soo Chang, Jin Hee Sohn, Dae Young Kang, Gyeong Hoon Kang, Myung Sook Kim, Woo Ho Kim, Jong Hee Nam, Woo Sung Moon, Sun Hoo Park, Cheol Jeun Park, Ro hyun Sung, Young Lyun Oh, Eun Sook Chang, Hee Kyung Chang, Mee Yon Cho, Kyung Ja Cho, Yong Il Kim; Korean J Pathol. 2001;35(1):14-19.

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Abstract PDF: BACKGROUND
This nationwide survey was undertaken to characterize the general pathological features of colorectal cancer in Korea, and especially to elucidate the geographical characteristics by means of their anatomical distribution.
METHODS
We analysed 1,676 colorectal cancers (from 1,602 patients) surgically resected in 1998 at 15 institutions from nine geographical sites in Korea.
RESULTS
The topographic incidence of colorectal cancer in seven out of the total nine geographical sites, was the highest in the rectum (32-54%); and those from Wonju and Cheongju were in the sigmoid colon (28% for both). The right colon cancer incidence was 42% in Wonju and 36% in Cheongju, while it was 17-22% in the other areas. The cecal cancer incidences in Wonju and in Taegu were 7% and 8%, respectively, but 0-4% in the other areas. As for histology, moderately differentiated adenocarcinoma was the most frequent (46-84%), except for in Wonju and Chonju, where the most predominant type was well differentiated (63% and 52%, respectively).
CONCLUSION
The incidence of right colon cancer was higher in Wonju and Cheongju, than in the other geographical sites. The cecal predilection was prominent in Taegu and Wonju. The Elucidation of geographical differences in degree of differentiation for tubular adenocarcinoma seems to require further cumulative study with strict guidelines.

Expression of E-cadherin, Matrix Metalloproteinase, and Vascular Endothelial Growth Factor in Squamous Cell Carcinoma and Adenocarcinoma of the Lung.: Ji Sun Song, Mee Yon Cho, Kwang Hwa Park, Soon Hee Jung, Kwang Gil Lee; Korean J Pathol. 2000;34(12):972-981.

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Abstract PDF: E-cadherin is a calcium-dependent epithelial adhesion molecule which plays a role in the initial step of invasion of cancer cells. The step that follows the migration of separated tumor cells is a proteolytic lysis of basement membrane and extracellular matrix by protease of epithelial and endothelial cells such as matrix metalloproteinase (MMP). Vascular endothelial growth factor (VEGF) is known to be an endothelial cell-specific powerful mitogen as well as a vascular permeability factor. This study is aimed to evaluate the correlation between expression of these factors and pathologic or clinical variables and the roles and prognostic significance of those factors in squmous cell carcinoma and adenocarcinoma of the lung. Immunohistochemical stains were performed for E-cadherin, MMP-2, and VEGF in surgically resected specimens from 90 patients with squmous cell carcinoma and adenocarcinoma of the lung. Mean age of the patients was 59.7 years. Histologic type was categorized into 56 cases of squamous cell carcinoma and 34 cases of adenocarcinoma. Mean survival period of the 35 patients was 54 months. The immunohistochemical stains for E-cadherin, MMP-2, and VEGF revealed positive reaction in 67 cases (74.4%), 43 cases (47.8%), and 34 cases (37.8%), respectively. The expression of E-cadherin was higher in adenocarcinoma (82.4%) than in squamous cell carcinoma (69.6%). MMP-2 was expressed in the tumor cells, especially those invading into the surrounding stroma. The expression of MMP-2 was significantly correlated with the survival rate (p<0.05). The expression of VEGF in the tumor cells was significantly higher in cases with lymph node metastasis (p<0.05). In conclusion, these findings suggest that the expression of MMP-2 and VEGF predict poor prognosis of patients with squmous cell carcinoma and adenocarcinoma of the lung and that VEGF may play a role in tumor metastasis.

Immunohistochemical Analysis of Transforming Growth Factor (TGF)-beta1 and TGF-beta Receptor II and Quantitative Analysis of TGF-beta1 mRNA during Multistep Hepatocarcinogenesis Induced by Diethylnitrosamine in Sprague-Dawley Rats.: Mee Yon Cho, Ju Han Lee, Yong Koo Kang, Nam Hee Won; Korean J Pathol. 1999;33(11):1009-1023.

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Abstract PDF: Transforming growth factor (TGF)-beta1 plays an important role in hepatocarcinogenesis and has been described as a useful tumor marker and one of the poor prognostic indicators in patients with hepatocellular carcinoma (HCC). To investigate the role and cellular localization of TGF-beta1 during multistep hepatocarcinogenesis we performed a quantitative analysis of TGF-beta1 mRNA and immunohistochemical expression of TGF-beta1 and TGF-beta receptor II (TGF-betarII) in female Sprague-Dawley rats. The experimental groups included neoplastic lesions produced by Solt-Farber's protocol, regenerating liver after partial hepatectomy, and normal control. Quantitative change of TGF-beta1 mRNA was analysed by competitive reverse-transcription polymerase chain reaction (RT-PCR). TGF-beta1 protein and TGF-betarII expression were evaluated by immunohistochemical stain. The discrete tumor nodules were detected on 14th day and then increased in number and size. Three HCCs were induced on 8th or 9th month. RT-PCR demonstrated TGF-beta1 mRNA band in all examples of the normal and regenerating liver, nodules and HCCs. Competitive RT-PCR displayed higher TGF-beta1 mRNA in nodules, HCCs and regenerating liver than in normal controls. Hepatocytes from control and regenerating livers showed weak immunoreactivity for TGF-beta1. In contrast, the cytoplasm of hepatocytes of nodules in 7th, 8th and 9th month and HCCs were intensely stained for TGF-beta1. Some sinusoidal cells showed immunoreactivity for TGF-beta1 in all experimental groups. In early phase of carcinogenesis, the cytoplasm of hepatocytes in liver of 12h, 1d and 3d showed transiently increased immunoreactivity for TGF-beta1 and The immunoreactivity decreased thereafter. TGF-beta1 mRNA was also detected in the neoplastic hepatocytes by in-situ hybridization. Although TGF-betarII expression was correlated with TGF-beta1 immunoreactivity during early phase of carcinogenesis, hepatocytes in most nodules in 7th, 8th, 9th month and carcinomas showed decreased or little immunoreactivity for TGF-betarII. Based on the above results, it is concluded that TGF-beta1 expression increases not only in precancerous nodules but also in HCCs and its increase seems to be correlated with decrease or loss of TGF-betarII expression although its mechanism remains unclear. Hepatocytes may be a major cellular source of TGF-beta1 during hepatocarcinogenesis.

Small Cell Osteosarcoma Similar to Ewing's Sarcoma in Histologic Findings and MIC2 Expression: A case report.: Yoon Mee Kim, Suk Woo Yang, Mee Yon Cho, Soon Won Hong, Byung Ho Choi; Korean J Pathol. 1999;33(3):204-209.

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Abstract PDF: Small cell osteosarcoma is a rare form of osteosarcoma and the histological differential diagnosis from other small round cell tumors (SRCTs) is difficult. The immunohistochemical stain for MIC2 has been considered an useful diagnostic marker for Ewing's sarcoma and primitive neuroectodermal tumors but recently, other SRCTs such as malignant lymphoma and embryonal rhabdomyosarcoma also showed positive reaction. Therefore, the usefulness of MIC2 must still be proven. We experienced a case of small cell osteosarcoma of the mandible in a 25-year-old man. Histologically, the tumor consisted of small round cells that resembled those of Ewing's sarcoma. Immunohistochemically, the tumor cells expressed diffuse strong positive reaction for MIC2 gene products. However, the scanty foci of lacy osteoid material between the tumor cells seemed to be diagnostic of osteosarcoma. The histologic and immunohistochemical findings of this case suggest close relationship between small cell osteosarcoma and Ewing's sarcoma.

p53 Mutation and Expression of Rb Protein in Germ Cell Tumors.: Ju Han Lee, Mee Yon Cho, Hae Hyeog Lee, Bom Woo Yeom, Nam Hee Won; Korean J Pathol. 1998;32(12):1074-1080.

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Abstract: We investigated the role of the tumor suppressor genes in the germ cell tumor. Immunohistochemistry (IHC) and polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) for p53 mutation were done in 46 cases of the germ cell tumor with paraffin embedded tissue. The immunohistochemical staining for Rb protein was also performed in the same specimens. The following results were obtained. The overexpression of the p53 protein was detected in 7 of 46 cases (15%). p53 mutation by PCR-SSCP was detected in 1 of 46 cases (2.2%). Expression of Rb protein was negative in 19 cases (41%). These results suggest that p53 mutation does not play an important role in the initiation and progression of germ cell tumors.

Flow Cytometric DNA Analysis of Gastrointestinal Stromal Tumors .: Mee Yon Cho, Soon Won Hong, Soon Hee Jung, Hogeun Kim, Chanil Park; Korean J Pathol. 1997;31(7):608-616.

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Abstract PDF: To evaluate the correlation between the histologic grade and DNA ploidy or proliferation index/S phase fraction (SPF) of gastrointestinal stromal tumors, we performed the DNA analysis using the flow cytometry. Paraffin embedded tissue samples of 57 gastrointestinal stromal tumors were used. The sites of the tumors were: stomach (28), small intestine (23), and large intestine(6). DNA index, proliferative index, and SPF by the flow cytomery were compared with histologic grade. The histologic grade of the gastric tumors were benign (12), borderline (10), and malignant (6). Those of the small intestinal timors were benign (2), borderline (13), and malignant(8). The large intestine were borderline (2), and malignant (4). In stomach, aneuploidy was found in 25.0% of benign, 40.0% of borderline, and 100% of malignant. And there was statistically significant correlation between the histologic grade and ploidy (p < 0.05). By contrast, small and large intestinal tumors showed more frequent aneuploidy in benign than in malignant. The proliferative index was correlated with the histologic grade in gastric tumors (p<0.05), but the SPF was not. In conclusion, the ploidy and proliferative index of gastric tumors are closely correlated to the histologic grade. However, aneuploidy in tumors of the small and large intestine were difficult to predict the malignancy.

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

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

Fine Needle Aspiration Cytology of Cervical Chordoma: A Case Report .: Kyung Moo Yang, Mee Yon Cho, Soon Hee Jung, Jeong Pyo Bong; Korean J Cytopathol. 1997;8(1):93-97.

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Abstract PDF: A case of cervical chordoma diagnosed by fine needle aspiration is discussed. A 41year-old male was admitted due to dyspnea on neck flexion. Radiologic image revealed a retrotracheal superior mediastinal solid mass. Aspiration cytology showed many clusters of oval or large polygonal cells having abundant eosinophilic or bubbly cytoplasm in an amorphous blue-gray mucoid background. The nuclei were round and showed size variation, coarse granular chromatin, and indistinct nucleoli. Some cells contained brown granular pigments in the cytoplasm. Mitoses were rarely found. The cytoplasm was strongly positive for PAS stain. Immunohistochemical stains using cell block revealed positive reaction for cytokerain, EMA, vimentin, and S-100 protein. The confirmative diagnosis was made by following excisional biopsy. Electron microscopic study revealed large pools of intracytoplasmic glycogen and microfilaments. This is the first case of cervical chordoma diagnosed by aspiration cytology to our knowledge in Korean literature.

Immunohistochemical Sdtudy of Cytokeratin and Epithelial Membrane Antigen Expression in Osteosarcoma.: Jong Yup Bae, Mee Yon Cho, Soon Hee Jung; Korean J Pathol. 1996;30(10):920-927.

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Abstract PDF: Immunohistochemical analysis of 24 paraffin-embedded osteosarcomas was studied to evaluate the expression of simple cytokeratin, basal cytokeratin and epithelial membrane antigen(EMA) according to the histologic subtypes and anatomical locations. Mean age of the patients was 18 years. Anatomical locations of the tumors were femur(8), tibia(10), humerus(4), lumbar spine(1), and zygomatic arch(1). Histologic subtypes included osteoblastic(14), fibroblastic(4), chondroblastic(4), epithelioid(1), and mixed osteoblastic and fibroblastic(1). All were positive in the immunohistochemical stain for vimentin. The expression of cytokeratin and/or EMA was found in 10 cases(41.7%) regardless of anatomical locations and histologic subtypes. Positive immunoreaction for EMA was demonstrated in osteoblastic(5), chondroblastic(2), epithelioid(1), and mixed osteoblastic and fibroblastic(1) types. Osteoblastic (2), chondroblastic(2), and epithelioid(1) types among them also showed immunoreactivity with anti-simple cytokeratin monoclonal antibody, NCL-5D3. The expression of basal cytokeratin (NCL-LL002) was found in two osteoblastic, one chondroblastic, one epithelioid, and one mixed osteoblastic and fibroblastic types. These findings indicate that cytokeratin and EMA immunoreactivity can not be regarded as an absolute specific marker of the epithelial origin of tumor and may also occur in osteosarcoma.

p53 Protein Expression in Infiltrating Ductal Carcinoma of the Breast.: Soon Hee Jung, Mee Yon Cho, Soo Yong Kim; Korean J Pathol. 1996;30(1):7-14.

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Abstract PDF: Overexpression of the nuclear phosphoprotein p53 is the most common genetic anomaly found in primary human cancer and mutation of the tumor suppressor gene p53 has been identified in breast cancer cell lines. In this study, we evaluated the prognostic significance of p53 protein expression in patients with mammary infiltrating ductal carcinoma and its correlation with histopathologic grade, lymph node status, tumor size, p53 protein expression and survival. Among 53 cases, p53 protein expression was detected in 26(49.1%) cases by immunohistochemistry. There was no correlation between p53 protein overexpression and histopathologic grade(p=0.09) or lymph node status(p=0.38) and between survival and histopathologic grade (p=0.68) or lymph node status(p=0.52). However, p53 protein expression was significantly correlated with survival(p=0.01) and patients with p53 protein-positive tumors showed poorer survival times. But Cox multivariate analysis showed the lymph node status is significant(p=0.01). The authors conclude that the presence of mutant p53 protein and lymph node status may serve a prognostic role, in a subset of mammary infiltrating ductal carcinoma cases.

Fine Needle Aspiration Cytology of Angiosarcoma of the Rib: A Case Report.: Hee Jung Kim, Mee Yon Cho, Soon Hee Jung, Kwang Gil Lee; Korean J Cytopathol. 1996;7(2):207-212.

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Abstract PDF: Angiosarcoma of the bone is rare with an incidence of 0.13%. It may be solitary or multiple. Its cytologic findings by FNA have rarely been reported. We report a case of angiosarcoma of the rib in a 66 year-old man. FNA revealed single or clusters of round to oval shaped cells in a hemorrhagic and myxoid background. The large central nuclei had irregular nuclear membrane, chromatin clumping and prominent nucleoli. The cytoplasm was scanty with an eosinophilic distinct cytoplasmic border. Erythrophagocytosis by malignant cells was also found. Histopathologic examination confirmed the diagnosis of angiosarcoma revealing irregular and com- plex anastomosing vascular channels lined by malignant round tumor cells, protruding into the lumen. Immunohistochemical staining revealed diffuse strong positive reaction to factor VIII-related antigen and CD31.

Infantile Hemangioendothelioma of the Liver: A histological and immunohistochemicalstudy of 4 cases.: Mee Yon Cho, Sun Hee Sung, Soon Hee Jung, Chanil Park; Korean J Pathol. 1995;29(2):145-151.

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Abstract PDF: A pathological study was performed on four cases of infantile hemangioendothelioma of the liver. All the patients were between the age of 1 -5 months and the tumors were typical hemangio-endotheliomas, type 1. The tumors were composed basically of two components; the endothelial cell proliferation and the myxoid matrix. The endothelial cells were cytologically innocuous and formed vascular channels of varying sizes and shapes from capillary to sinusoidal and cavernous vessels. Fibrosis of the matrix, albeit not a major component of the tumor, was found particularly near the center. Immunohistochemically, CD31 was expressed strongly in almost all endothelial cells, in contrast to the stain for von Willebrand factor which was only focally and weakly positive. Alpha-fetoprotein was expressed in hepatocytes within the tumor or in hepatocytes around the tumor. Intratumoral bile duct structures were located mainly at peripheral portion. The results indicated that the type I infantile hemangioendothelioma is a tumor of endothelial cells and myxoid stroma, and that the endothelial cells undergo gradual maturation to form sinusoidal and cavernous vessels in accordance with gradual fibrosis of the myxoid stroma.

Peritoneal Diffuse Anaplastic Malignant Mesothelioma Simulating Anaplastic Carcinoma.: Mee Yon Cho, Soon Hee Jung, Woo Ick Jang, Dong Su Cha; Korean J Pathol. 1994;28(2):206-209.

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Abstract PDF: A case of diffuse malignant mesothelioma of peritoneum which was difficult to distinguish from metastatic anaplastic carcinoma or malignant melanoma was presented. The patient was a 50 year-old woman and complained of an abdominal pain and ascites for 20 days. Histologically, the tumor cells showed highly anaplastic appearance with sheet-like arrangement without any papillary or tubular structure. They stained Positive for cytokeratin and vimentin and negative for CEA, S-100 protein and melanoma associated antigen. A few cells within the tumor showed Positive reactivity to desmin. Ultrastructurally, the tumor cells had characteristic findings of mesothelioma such as long, exuberant, wavy microvilli with 10 to 12 of length/diameter ratio. The patient died 3 months after the diagnosis in spite of intraperitoneal chemotherapy.

Histologic Grading of Astrocytic Neoplasms in Conjunction with Evaluation of Proliferative Activity Using Ag-NORs Count PCNA Expression, and Flow CYtometric DNA Analysis.: Mee Yon Cho, Soon Hee Jung, Tal Seung Kim, Yong Pyo Han; Korean J Pathol. 1994;28(1):49-55.

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Abstract PDF: Although the histologic grade of astrocytic neoplasms of the brain have been used as a prognostic factor, the lack of an objective criteria is possible to create the disagreement of classification. We evaluated 25 cases of astrocytic neoplasms of brain to document the usefulness of prolifera-tive potential of tumor as a prognostic indicator and the correlation with histologic grade by Nils Ringertz. The Ringertz's classification was relatively simple in an application among the variable systems and easy to define the differentiate from grade to grade. The examined cases were com-prised of 7 astrocytomas, 9 anaplastic astrocytomas and 9 glioblastoma multif6rmes. The prolife-rative potential of tumors were measured by Ag-NORs count, PCNA labeling index and flow cytometric analysis. The mean numbers of Ag-NORs per cell and PCNA labeling index were sig-nificantly differ among each histologic grade. In addition, abnormal DNA content and high prolif-erative index were frequently identified in anaplastic astrocytoma and glioblastoma multiforme. Therefore, the Ag-NORs counts, PCNA labeling index, DNA index and proliferative index were well correlated with the histologic grade.

Primary Cardiac Angiosarcoma: A case report and rewiew of literture.: Mee Yon Cho, Soon Hee Jung, Woo Ick Yang, Kyung Hoon Choe, Chong Kook Lee; Korean J Pathol. 1993;27(4):397-401.

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Abstract PDF: We report a case of primary cardiac angiosarcoma in a 35 year-old woman. She presented with dyspnea, facial edema and neck vein distension during 1 month. The oval round large mass(8x4 cm) filling the right atrium infiltrated into the entire thickness of the lateral wall and extended to the vena cava and ventricle. The interatrial septum and pericardium seemed to be intact. Despite the surgical excision and adjuvant chemo-and radiotherapy, the patient died 8 months later due to tumor recurrence. The histologic findings of tumor varied from benign looking capillary proliferation mimicking granulation tissue to sarcoma composed of spindle cells. But anastomosing vascular channels lined by anaplastic polygonal cells and intracytoplasmic lumen containing red blood cells were characteristic findings. These tumor cells showed positive reaction to endothelial cell antigen and factor VIII-related antigen. The intercellular junctional complex and vascular channels formed by cytoplasmic process of tumor cells were identified by the ultrastructural study.

Comparative Assessment of Immunohistochemical and Zieh1-Neelsen Stains for Demonstration of Mycobacterium Tuberculosis.: Mee Yon Cho, Soon Hee Jung, Woo Ick Yang; Korean J Pathol. 1993;27(3):243-248.

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Abstract PDF: To obtain a useful method for the identification of mycobacteria in tissue section, we evaluated 118 cases of tuberculosis: 48 pulm onary, 14 lymph nodal and 56 synovial tuberculosis. Seventy nine of these cases underwent the culture study. Sections stained with anti-Mycobacterium bovis were compared with the results of the Zieh1-Neelsen stain and culture. The immunohistochemical stain for Mycobacterium bovis in al examined cases was not any more sensitive than the Zieh1-Neelsen stain(p>0.05). Neverthless, the immunohistochemical stain was a useful method for the localization of mycobacteria because of the striking contrast between its background and the wider dimension of a positive area. Immunoreactive areas demonstrated a few intact mycobacteria showing a positive reaction in the Zieh1-Neelsen stain. In conclusion, double staining method using the immunohischemical stain for Mycobacterium bovis and the Zieh1-Neelsen stain is an efficient technique in oder to confirm the diagnosis of tuberculosis.

A Study on Immunohistochemical Stain for S-100 Protein, HMB 45 and Proliferating Cell Nuclear Antigen(PCNA) of Spitz Nevus Compared with Benign Nevus and Malignant Melanoma.: Mee Yon Cho, Kwang Gil Lee, Myung Wook Kim; Korean J Pathol. 1992;26(6):552-560.

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Abstract PDF: The differential diagnosis between Spitz nevus and malignant melanoma is difficult due to similar histologic findings. To obtain the useful aids for the differential diagnosis between two diseases, we studied 13 cases of Spitz nevus, 8 benign nevi of compound and intradermal, and 9 melanomas of primary and metastatic, using the immunohistochemical stain for S-100 protein, HMB.45 and proliferating cell nuclear antigen(PCNA). The staining pattern and intensity of S-100 protein showed homogenously strong positive reactivity in all cases. The frequency of HMB.45 positive cell in Spitz nevus was significantly lower than that in melanoma. When compared with the usual compound and intradermal nevi, Spitz nevi showed more significantly positive reaction in the dermal component of nevus cells. The expression of PCNA was higher in melanoma than in Spitz nevus. The immunohistochemical stains for HMB.45 and PCNA are considered as a useful methods for differentiation between Spitz nevus and melanoma, while stain for S-100 protein is not helpful.

Pathological Predictor for Prognosis in Gastrointestinal Mesenchymal Neoplasms.: Mee Yon Cho, Ho Guen Kim, Chan Il Park, Yoo Bock Lee; Korean J Pathol. 1991;25(6):528-538.

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Abstract PDF: To evaluate the prognostic predictor and clinicopathologic characteristics of the gastrointestinal (GI) mesenchymal neoplasm, we examined 75 cases of GI mesenchymal tumors surgically resected during 8 years from 1983 to 1990. Various histological parameters referrable to the prognosis, including the Ag-NORs count, were analysed. Fifty cases were followed-up for 1 to 7 years. Sixteen out of these fifty cases died during this period. The location of tumor was the stomach in 33 cases, the small intestine in 31 cases and the large intestine in 11 cases, and the tumor size was variable from 2 to 35 cm in diameter. The GI mesenchymal neoplasm appeared as an extraluminal mass in 50 cases, an intramural mass in 17 cases, and an intraluminal mass in 8 cases. Each tumor was composed of spindle or epithelioid cells, the former cell type being more common than the latter (45 vs 30 cases). Mitotic count of the tumor showed the best correlationship with the survival of patients(p<0.05), although the tumor size and necrosis appeared to have some values. The Ag-NORs count was variable and was not significantly correlated with the patient's prognosis(p>0.05). These results indicate that the mitotic count is the most valuable pathological predictor for the prognosis in GI mesenchymal neoplasms.

Low-grade Uterine Endometrial Stromal Sarcoma Resembling Ovarian Sex-Cord Tumor : A case report.: Mee Yon Cho, Kyu Rae Kim, Woo Hee Jung, Hyeon Joo Jeong, Kyi Beum Lee; Korean J Pathol. 1991;25(5):476-480.

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Abstract: A case of low-grade endometrial stromal sarcoma resembling ovarian sex-cord tumor in the uterus of a 43-year-old woman is described. This tumor belongs to the group II category of uterine tumors resembling ovarian sex-cord tumor described by Clement and Scully, and the epithelial-like elements show prominent smooth muscle differentiation, proved by immunoreactivity for desmin and actin. The patient did not receive any adjuvant therapy; she is alive and well without recurrence 8 months postoperatively.

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