Journal of Pathology and Translational Medicine

Original Article

The Use of the Bethesda System for Reporting Thyroid Cytopathology in Korea: A Nationwide Multicenter Survey by the Korean Society of Endocrine Pathologists: Mimi Kim, Hyo Jin Park, Hye Sook Min, Hyeong Ju Kwon, Chan Kwon Jung, Seoung Wan Chae, Hyun Ju Yoo, Yoo Duk Choi, Mi Ja Lee, Jeong Ja Kwak, Dong Eun Song, Dong Hoon Kim, Hye Kyung Lee, Ji Yeon Kim, Sook Hee Hong, Jang Sihn Sohn, Hyun Seung Lee, So Yeon Park, Soon Won Hong, Mi Kyung Shin; J Pathol Transl Med. 2017;51(4):410-417. Published online June 14, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.05

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Background
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has standardized the reporting of thyroid cytology specimens. The objective of the current study was to evaluate the nationwide usage of TBSRTC and assess the malignancy rates in each category of TBSRTC in Korea.
Methods
Questionnaire surveys were used for data collection on the fine needle aspiration (FNA) of thyroid nodules at 74 institutes in 2012. The incidences and follow-up malignancy rates of each category diagnosed from January to December, 2011, in each institute were also collected and analyzed.
Results
Sixty out of 74 institutes answering the surveys reported the results of thyroid FNA in accordance with TBSRTC. The average malignancy rates for resected cases in 15 institutes were as follows: nondiagnostic, 45.6%; benign, 16.5%; atypical of undetermined significance, 68.8%; suspicious for follicular neoplasm (SFN), 30.2%; suspicious for malignancy, 97.5%; malignancy, 99.7%.
Conclusions
More than 80% of Korean institutes were using TBSRTC as of 2012. All malignancy rates other than the SFN and malignancy categories were higher than those reported by other countries. Therefore, the guidelines for treating patients with thyroid nodules in Korea should be revisited based on the malignancy rates reported in this study.

Citations

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Welcoming the new, revisiting the old: a brief glance at cytopathology reporting systems for lung, pancreas, and thyroid
Rita Luis, Balamurugan Thirunavukkarasu, Deepali Jain, Sule Canberk
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Uiju Cho, Yourha Kim, Sora Jeon, Chan Kwon Jung
Applied Immunohistochemistry & Molecular Morphology.2022; 30(5): 389. CrossRef
Malignancy rates in thyroid nodules: a long-term cohort study of 17,592 patients
M Grussendorf, I Ruschenburg, G Brabant
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Huy Gia Vuong, Hanh Thi Tuyet Ngo, Andrey Bychkov, Chan Kwon Jung, Trang Huyen Vu, Kim Bach Lu, Kennichi Kakudo, Tetsuo Kondo
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Gamze ÇITLAK, Bahar CANBAY TORUN
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Hee Young Na, Jae Hoon Moon, June Young Choi, Hyeong Won Yu, Woo-Jin Jeong, Yeo Koon Kim, Ji-Young Choe, So Yeon Park, Paula Soares
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Brief Case Report

Digital Papillary Carcinoma: Sharon Lim, Inju Cho, Mi Ja Lee; Korean J Pathol. 2014;48(6):438-441. Published online December 31, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.6.438

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PDF

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Original Articles

Early Colorectal Epithelial Neoplasm in Korea: A Multicenter Survey of Pathologic Diagnosis: Yun Kyung Kang, So-Young Jin, Mee Soo Chang, Jung Yeon Kim, Gyeong Hoon Kang, Hye Seung Lee, Jin Hee Sohn, Ho Sung Park, Kye Won Kwon, Mi Jin Gu, Young Hee Maeng, Jong Eun Joo, Haeng Ji Kang, Hee Kyung Kim, Kee-Taek Jang, Mi Ja Lee, Hee Kyung Chang, Joon Mee Kim, Hye Seung Han, Won Ae Lee, Yoon Jung Choi, Dong Wook Kang, Sunhoo Park, Jae Hyuk Lee, Mee-Yon Cho; Korean J Pathol. 2013;47(3):245-251. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.245

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Abstract PDF

Background

The incidence of early colorectal epithelial neoplasm (ECEN) is increasing, and its pathologic diagnosis is important for patient care. We investigated the incidence of ECEN and the current status of its pathologic diagnosis.

Methods

We collected datasheets from 25 institutes in Korea for the incidence of colorectal adenoma with high grade dysplasia (HGD) and low grade dysplasia in years 2005, 2007, and 2009; and early colorectal carcinoma in the year 2009. We also surveyed the diagnostic terminology of ECEN currently used by the participating pathologists.

Results

The average percentage of diagnoses of adenoma HGD was 7.0%, 5.0%, and 3.4% in years 2005, 2007, and 2009, respectively. The range of incidence rates of adenoma HGD across the participating institutes has gradually narrowed over the years 2005 to 2009. The incidence rate of early colorectal carcinoma in the year 2009 was 21.2%. The participants did not share a single criterion or terminology for the diagnosis of adenoma HGD. The majority accepted the diagnostic terms that distinguished noninvasive, mucosal confined, and submucosal invasive carcinoma.

Conclusions

Further research requirements suggested are a diagnostic consensus for the histopathologic diagnosis of ECEN; and standardization of diagnostic terminology critical for determining the disease code.

Citations

Citations to this article as recorded by

Diminutive and Small Colorectal Polyps: The Pathologist's Perspective
Yun Kyung Kang
Clinical Endoscopy.2014; 47(5): 404. CrossRef

Significance of the Expression of Cathepsins B, H, & L in Colonic Epithelial Neoplasms.: Jae Young Sim, Mi Ja Lee, Keun Hong Kee; Korean J Pathol. 2009;43(5):408-412.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.408

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Abstract PDF: BACKGROUND
Cathepsin is associated with tumorigenesis, tumor invasion and metastasis through its ability to induce degradation of extracellular matrix components.
METHODS
To investigate the correlation between cathepsin expression and tumor progression, invasion depth or nodal metastasis, immunohistochemical staining for cathepsins B, H and L were done on 20 hyperplastic polyps, 48 adenomas, and 67 adenocarcinomas of the colon. Evaluation of the expression of cathepsins B, H and L was based on the percentage of neoplastic cells that stained positive for any given cathepsin.
RESULTS
Cathepsin B expression was significantly higher in adenocarcinomas than adenomas (29.33 vs 5.48%), but was not associated with the degree of differentiation, depth of invasion and nodal status of the tumors. Expression of cathepsins H and L was absent or low in both adenomas and adenocarcinomas. CONCLUSIONS: We suggest that cathepsin B is involved in progression of a subset of colonic adenomas, while cathepsins H and L are not.

A Histopathologic Studies for Endometrium of Early Pregnancy.: Mi Ja Lee, Kenn Hong Kee, Chae Hong Suh, Ho Jong Jeon; Korean J Pathol. 1995;29(4):492-501.

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Abstract PDF: Endometrium of early pregnancy were compared with nonpregnant endometnum by inimunohistochemical and ultrastructural techniques with respect to glandular and stromal elements of endometrium. The results obtained were as follows: 1. The AS cell in decidua has all the features of actively secreting glandular epithelium and shows the pronounced arrays of glandular endoplasmic reticulum and moderate numbers of ribosomes ultrastructually. Therefore the AS cell indicate considerable protein production, presumably contributing to both cell gowth and the production of secretions. 2. The process of decidualization can be characterized morphologically and immunohistochemically by the accumulation of basement membrane-like materials, such as laminin and type IV collagen which may be related to the hormonal stimulation occuring during pregnancy and trophoblastic attachment. 3. The decidual cells show strong positive for vimentin and some large mature decidual cells show weakly positive for lysozyme and cti- antitrypsin, which might represent more the sequential differentiation of stromal cells into decidual cells than origin of histiocytes. 4. Immunoreactivity with S-100 protein was found in glandular and stromal cells of decidua but negative in endometrium of nonpregnant women. So some humoral factors related to pregnancy stimulate expression of S-100 protein in glandular and stromal cells of decidua.

Case Reports

VATER Association: Three autopsy case reports with imusual defects.: Mi Ja Lee, Myeong Cherl Kook, Je G Chi; Korean J Pathol. 1995;29(5):678-683.

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Abstract: VATER association represents vertebral defects, anal atresia, tracheo-esophageal fistula with without esophageal atresia, renal defects and radial limb dysplasia. The probability of the simultaneous occurrence of any three of these defects is so unlikely that it suggests a sporadic non-random association. This non-random association appears to be related to some chromosomal anomalies, the caudal regression syndrome, mesodermal defects in early developmental period or the matemal use of sex hormones during embryogenesis. We report three autopsy cases of the VATER association that showed most of the known major and minor defects as well as an unusual concurrence of other defects, i.e., scoliosis, talipes varus, absent penis, urethral agenesis and stenosis, rectourethral fistula, rib anomaly, single umbilical artery, Meckel's diverticulum, diaphragmatic hemia, absent rectum, short neck, simian crease, low set ear, and hypoplastic lung.

Suprasellar Rathke Cleft Cyst: A case report.: Mi Sook Lee, Yu Kyeong Jeong, Mi Ja Lee, Keun Hong Kee; Korean J Pathol. 1996;30(7):649-651.

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Abstract PDF: We report a case of a large asymptomatic Rathke cleft cyst in a 14-year-old boy. This cyst was of considerable size, measuring 2x1.8x1.8 cm, but did not produce any symptoms and was confined to the suprasellar area. The cyst wall was lined by pseudostratified ciliated columnar epithelium with goblet cells. The lining epithelium of the Rathke cleft cyst was immnoreactive for cytokeratin, EMA and CEA.

Endothelial Cyst of the Adrenal Gland: Report of a case.: Sung Chul Lim, Mi Sook Lee, Yun Sin Kim, Keun Hong Kee, Yu Kyung Jeong, Mi Ja Lee, Soon Bong Chung; Korean J Pathol. 1996;30(8):742-745.

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Abstract PDF: Adrenal cysts are rare lesion that usually present themselves as an incidental finding during surgery, or at the time of autopsy. The cysts are usually small, seldom exceeding 10cm in diameter, and are generally asymptomatic. However, they present a difficult problem in differentiation between benign and malignant lesions of the adrenal gland. In the differential diagnosis, other cystic lesions of the upper abdomen must also be considered, including hepatic, splenic, renal and pancreatic cysts. Herein we report a case of endothelial cyst of lymphangiomatous type of the adrenal gland which was detected in a 44-year-old male patient during a routine health examination by ultrasonography as a pancreatic pseudocyst. Gross examination revealed multiple separate but continuous cysts, measuring 10.6x8x7cm in dimension. Within the wall, compressed adrenal cortex was noted. Microscopically, fibrous wall containing hypertrophied smooth muscle lined by endothelial cells was also noted. We reviewed literatures of the adrenal cyst and report a case.

Original Article

Establishment and Characterization of an Epstein-Barr Virus-negative B-cell Line from a Patient with Dissemination of Peripheral Blood and Bone Marrow by Malignant Lymphoid Cell.: Ho Jong Jeon, Mi Ja Lee, Yu Kyung Jeong, Yoo Hwan Park, Choon Hae Chung, Yoon Kyung Oh, Chul Heel Choi, Sang Woo Cheong; Korean J Pathol. 1996;30(9):792-809.

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Abstract PDF: A human malignant lymphoid cell line(JeKo-1) was established from a Korean patient with retroperitoneal tumor presenting peripheral blood and bone marrow involvement by malignant lymphoid cells. This cell line was established from peripheral blood, and the cell line had the identical immunophenotypic features as malignant cells from the peripheral blood. The established cell line had features of a mature B-cell phenotype with no evidence for commitment to other lineages. The JeKo-1 grows in suspension with a doubling time of 33 hours. By light and electron microscopic examination, the established cells had a follicular center showing, a small, cleaved, lymphoid appearance, and had a large amount of cytoplasm containing few vacuoles and an irregular cytoplasmic membrane. Immunophenotypic analyses with monoclonal antibodies using flow cytometry showed a monoclonal IgM kappa and CD5- B-cell phenotype. The cells were non-reactive for T-cells and myeloid/monocyte antigens, and no evidence of Epstein-Barr virus nuclear antigen by polymerase chain reaction. DNA analysis showed a hypodiploid stemline with a DNA index of 0.83. The established cells were strongly reactive for bcl-2 and c-myc onco-protein, but lacked expression of multidrug resistance gene protein, p-glycoprotein by Western blot analysis. Karyotypic analysis of JeKo-1 showed 40-41 chromosomes. This cell line should be a valuable tool to study the dissemination of malignant lymphoma into the peripheral blood and bone marrow.

Case Report

Bilateral Elastofibroma: Report of a case.: Sung Chul Lim, Mi Sook Lee, You Kyung Jeong, Yun Shin Kim, Hyun Jong Park, Mi Ja Lee; Korean J Pathol. 1997;31(6):589-591.

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Abstract PDF: Elastofibroma is a rare benign tumor-like condition manifesting as firm and spherical mass with poorly circumscribed margins of fibroelastic tissue, occuring in the subscapular region or the chest wall of elderly persons. It is not a true neoplasm but rather a reactive or degenerative process causing abnormal elastogenesis. It is unilateral in the majority of cases and the right side is affected more commonly than the left. We report a case of bilateral elastofibromas removed from both subscapular regions of a 73-year-old female farmer. She was presented with tender masses on the bilateral subscapular areas for seven years. Microscopically, it consisted of a mixture of intertwining broad eosinophilic collagen bundles and elastic fibers associated with a few fibroblasts and mature fat cells. The elastic fibers had a degenerated beaded appearance or were fragmented into serrated globules in a linear arrangement.

Original Articles

Establishment and Characterization of a Small Cell Lung Cancer Cell Line(JePa-1).: Mi Ja Lee, Ho Jong Jeon, Jong Hoon Chung; Korean J Pathol. 1997;31(8):695-710.

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Abstract PDF: Lung cancer is the most common malignant tumor worldwide and its incidence continues to rise each year. Recent development of molecular biologic method has led to advances in determining the etiologic factors of lung cancer and the establishment of cell lines has provided a lot of information on the through chemosensitivity, radiation biology studies, cytogenetics, and molecular biologic studies, which permits improved treatment for lung cancer. We established a small cell lung cancer cell line, designated JePa-1, obtained from malignant pericardial effusion of small cell lung cancer patient and characterized its morphologic and molecular biologic features. the JePa-1 cell line grew relatively slowly (doubling time 45hrs) as very loosely adherent floating aggregates growing in small clumps with distinct cell outlines and intertwined cords. Also JePa-1 cell line secreted antidiuretic hormones. Electronmicroscopic examination revealed that JePa-1 cell line and xenografts contained electron dense core granules, characteristic of being of neuroendocrine origin. To investigate the tumorigenic capacity, the JePa-1 cell line was injected into SCID and nude mice. Tumors taken from xenografts were observed in 3 out of 4 of the SCID mice and 2 out of 4 of the nude mice. The histologic characteristics of the xenografts were similar to those of the cell line and the original cytologic finding of the pericardial fluid, suggesting small cell carcinoma. The results of immunohistochemical markers showed reactivity for Rb protein, c-myc, TGF-alpha, TGF-beta , EGFR, keratin, NSE, chromogranin, and EMA. The DNA ploidy and the index of the JePa-1 cells was tetraploid and 2.13, respectively. The positive rate for the Rb, c-myc and K-ras proteins of the JePa-1 cell line were 98.9%, 99.3%, and 99.7% respectively as determined by flow cytometry. Cytogenetic analysis using the G-banding technique showed 65 chromosomes with various numerical and structural abnormalities. On examination of the expression of TGF-alpha, TGF-beta , and EGFR by PCR, only the EGFR was positive Through the establishment of JePa-1 cell line, we report in this paper the characterization of a small cell lung cancer such as morphologic and immunocytochemical features, growth characteristics in culture, hormone production, expression of oncoprotein and several growth factors, tumorigenicity, chromosomal abnormalities, and DNA ploidy and index. The JePa-1 cell line will be valuable in vitro studies for the etiology, treatment and the prognostic factors in small cell lung cancer.

Correlation of Expression of CD44, p53 and bcl-2 Protein, DNA Ploidy Pattern, and Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast.: Mi Ja Lee, Ho Jong Jeon, Kweon Cheon Kim; Korean J Pathol. 1999;33(12):1152-1162.

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Abstract PDF: In this study of 64 cases of breast cancer with a clinical follow-up period of more than 5 years, several prognostic factors were evaluated. The purpose of this study was to determine whether any one parameter or group of parameters serves as adequate predictors of tumor behavior and patient's prognosis. Several prognostic factors included clinicopathological variables (patient's age, histologic grade, status of lymph node (LN) metastasis, and tumor size), expression of estrogen receptor (ER), progesterone receptor (PR), p53, bcl-2 and CD44 by immunohistochemistry, and DNA ploidy pattern. The results showed that the expression of ER and PR had a significant inverse correlation with the histologic grade (ER, p=0.05; PR, p<0.05). The expression of p53 protein showed a significant relationship with high histologic grade of tumor (p<0.05). The expression of bcl-2 protein was preferably seen in low histologic grade of tumor (p<0.05) and significantly associated with ER positive or PR positive tumors (ER, p<0.05; PR, p<0.05). This results suggest that bcl-2 protein might play significant roles in ER and PR. The CD44 expression showed a significant relationship with tumor size (p<0.05). The large size and aneuploidy pattern of tumor had a tendency to be associated with shorter patient survival. Cox's multivariate analysis showed that overall survival was affected by LN metastasis because of the shorter survival in patients with LN metastasis. In conclusion, tumor size, DNA ploidy pattern, and LN metastasis were themselves significant predictors of breast cancer survival rate.

Significance of Expression of p16, Cyclin D1, Rb, and p53 Protein and Correlation with Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast.: Mi Ja Lee, Ho Jong Jeon, Kweon Cheon Kim; Korean J Pathol. 2000;34(4):288-299.

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Abstract PDF: The retinoblastoma (Rb)/cyclin D1/p16 pathway is an important constituent of cell cycle regulation. Perturbations in this pathway due to a variety of genetic aberrations have been reported in many human cancers including breast cancer. We examined the significance of immunoexpression of p16 protein, cyclin D1 protein, Rb protein (pRb), and p53 protein in 128 cases of invasive breast carcinoma. The results were correlated with survival rate and clinicopathological variables, including age, histologic grade, lymph node status, tumor size, estrogen receptor (ER), and progesterone receptor (PR) content. Abnormal expressions of p16 and pRb which were defined as negative staining were seen in 21% and 43% of tumors, respectively. There was a significant inverse relationship between p16 and pRb expression. There was no correlation between p16 staining and any other parameters, including survival rate, cyclin D1, p53, and clinicopathologic variables. Surprisingly, there was a trend for tumors which were positive for pRb to be grade III ductal carcinomas. Cyclin D1 positivity was noted in 46% of cases. The expression of cyclin D1 protein was significantly higher in lower histologic grade, higher ER and PR expression. The expression of p53 protein showed a significant correlation with high tumor grade. In a Cox multivariate analysis, neither p16, pRb, cyclin D1 nor p53 was an independent predictor, but tumor size and lymph node status were independent predictors of patient outcome.

Expression of Chromogranin A, Cathepsin D, Cyclin D1 and p53 proteins in Colorectal Adenocarcinoma.: Chae Hong Suh, Mi Ja Lee, Sung Kang Cho; Korean J Pathol. 2001;35(1):7-13.

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Abstract PDF: BACKGROUND
The purpose of this study is to assess the roles of chromogranin A, cathepsin D, cyclin D1 and p53 protein expression in colorectal tumorigenesis.
METHODS
83 colorectal cancer and 12 villotubular adenoma tissue specimens were investigated by immunohistochemical staining for chromogranin A, cathepsin D, cyclin D1 and p53 protein. Clinicopathologic values (tumor size, histologic grade, Astler-Coller stage and lymph node metastasis) were compared with the incidence of chromogranin A, cathepsin D, cyclin D1 and p53 protein expression in colorectal adenocarcinomas.
RESULTS
Statistically significant correlation was noted between the expression of chromogranin A and histologic grade (p<0.05). The incidence of positive cathepsin D expression was increased with tumor size (p<0.05), and there was a statistically significant correlation between histologic grade and cathepsin D expression (p<0.005). There were no statistically significant correlations among cyclin D1 expression and tumor size, histologic grade, stage and lymph node metastasis. Patients with lymph node metastasis had a high incidence of positive p53 protein expression compared to those without this finding (p<0.001).
CONCLUSION
It is suggested that chromogranin A, cathepsin D, and p53 protein are useful variables for the prognostic assessment of colorectal adenocarcinoma. The p53 protein seems to involve the metastatic ability of colorectal adenocarcinomas. Also, the expression of cathepsin D, cyclin D1, and p53 protein may play an important role in the tumorigenesis and progression of the colorectal adenoma-carcinoma sequence.

Immunocytochemical Characteristics of the Short-term cultured Mesothelial Cells.: Ho Jong Jeon, Mi Ja Lee, Mi Sook Lee, Yu Kyung Jeong, Young Mi Lee, Hyung Ho Choi; Korean J Cytopathol. 1995;6(2):106-115.

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Abstract PDF: Reactive human mesothelial cells were examined by immunocytochemical stain with intermediate filaments(cytokeratin [CK1, CK7, CK8, CK18, CD19/, vimentin, desmin, actin), epithelial membrane antigen, carcinoembryonic antigen(CEA), MHC class II antigen(HLA-DR), LeuM-1(CD15), alpha1-antitrypsin(ACT), alpha1-antichymotrypsin (ACHT), CD68(KP-1) and FcgammaRIII(CD16). The mesothelial cells were isolated from patients with liver cirrhosis and pleural effusion, and short-term cultured in RPMI 1640 media containing 10% heat inactivated fetal calf serum and 1% identical supernatant fluid of the patients' transudates. The results obtained are as follows. 1. The cultured-reactive mesothelial cells were positive for the protein of cytoskeleton such as cytokeratin and vimentin, but negative for desmin and actin. The resting mesothelial cells showed positive reactions for cytokeratin, but negative for vimentin, desmin and actin. 2. The primary antibodies to the cytokeratin were strongly reactive for CK1, CK8 and CK18 but negative for CK7 and CK19 in both reactive and resting mesothelial cells. 3. Resting mesothelial cells showed negative reactions for CEA, but strong positive reactions in cultured-reactive mesothelial cells. 4. The markers for the monocytes\histiocytes (CD11b, CD14, CD16, CD68, lysozyme and alpha1-antitrypsin and alpha1-antichymotrypsin) were nonreactive in resting mesothelial cells, but lysozyme and alpha1-antitrypsin were weakly reactive in reactive and proliferative mesothelial cells. 5. MHC Class II molecule(HLA-DR antigen) was negative in both resting and reactive mesothelial cells. These results suggest that the short-term cultured, reactive mesothelial cells show a newly aberrant expression of the vimentin and carcino-embryonic antigen. The reason of the aberrant expression of the intermediate filament and oncofetal antigen in reactive and proliferative mesothelial cells should be further evaluated.

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