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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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  • 230 Download
  • 25 Web of Science
  • 23 Crossref
AbstractAbstract PDF
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

Citations to this article as recorded by  
  • High Rates of Unnecessary Surgery for Indeterminate Thyroid Nodules in the Absence of Molecular Test and the Cost-Effectiveness of Utilizing Molecular Test in an Asian Population: A Decision Analysis
    Man Him Matrix Fung, Ching Tang, Gin Wai Kwok, Tin Ho Chan, Yan Luk, David Tak Wai Lui, Carlos King Ho Wong, Brian Hung Hin Lang
    Thyroid®.2025; 35(2): 166.     CrossRef
  • Inconclusive cytology results of fine-needle aspiration for thyroid nodules: the importance of strict guideline implementation
    Sangwoo Cho, Kyunghwa Han, Jung Hyun Yoon, Vivian Youngjean Park, Miribi Rho, Jiyoung Yoon, Jin Young Kwak
    Ultrasonography.2025; 44(4): 285.     CrossRef
  • Improved Diagnostic Accuracy of Thyroid Fine-Needle Aspiration Cytology with Artificial Intelligence Technology
    Yujin Lee, Mohammad Rizwan Alam, Hongsik Park, Kwangil Yim, Kyung Jin Seo, Gisu Hwang, Dahyeon Kim, Yeonsoo Chung, Gyungyub Gong, Nam Hoon Cho, Chong Woo Yoo, Yosep Chong, Hyun Joo Choi
    Thyroid®.2024; 34(6): 723.     CrossRef
  • 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
    Journal of Pathology and Translational Medicine.2024; 58(4): 165.     CrossRef
  • Fine needle aspiration cytology diagnoses of follicular thyroid carcinoma: results from a multicenter study in Asia
    Hee Young Na, Miyoko Higuchi, Shinya Satoh, Kaori Kameyama, Chan Kwon Jung, Su-Jin Shin, Shipra Agarwal, Jen-Fan Hang, Yun Zhu, Zhiyan Liu, Andrey Bychkov, Kennichi Kakudo, So Yeon Park
    Journal of Pathology and Translational Medicine.2024; 58(6): 331.     CrossRef
  • Predictors of Malignancy in Thyroid Nodules Classified as Bethesda Category III
    Xiaoli Liu, Jingjing Wang, Wei Du, Liyuan Dai, Qigen Fang
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Risk stratification of indeterminate thyroid nodules by novel multigene testing: a study of Asians with a high risk of malignancy
    Chunfang Hu, Weiwei Jing, Qing Chang, Zhihui Zhang, Zhenrong Liu, Jian Cao, Linlin Zhao, Yue Sun, Cong Wang, Huan Zhao, Ting Xiao, Huiqin Guo
    Molecular Oncology.2022; 16(8): 1680.     CrossRef
  • CD56 Expression in Papillary Thyroid Carcinoma Is Highly Dependent on the Histologic Subtype: A Potential Diagnostic Pitfall
    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
    European Thyroid Journal.2022;[Epub]     CrossRef
  • Subclassification of the Bethesda Category III (AUS/FLUS): A study of thyroid FNA cytology based on ThinPrep slides from the National Cancer Center in China
    Huan Zhao, HuiQin Guo, LinLin Zhao, Jian Cao, Yue Sun, Cong Wang, ZhiHui Zhang
    Cancer Cytopathology.2021; 129(8): 642.     CrossRef
  • Effect of the Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) Nomenclature Revision on Indian Thyroid Fine-Needle Aspiration Practice
    Chanchal Rana, Pooja Ramakant, Divya Goel, Akanksha Singh, KulRanjan Singh, Suresh Babu, Anand Mishra
    American Journal of Clinical Pathology.2021; 156(2): 320.     CrossRef
  • Comprehensive DNA Methylation Profiling Identifies Novel Diagnostic Biomarkers for Thyroid Cancer
    Jong-Lyul Park, Sora Jeon, Eun-Hye Seo, Dong Hyuck Bae, Young Mun Jeong, Yourha Kim, Ja Seong Bae, Seon-Kyu Kim, Chan Kwon Jung, Yong Sung Kim
    Thyroid®.2020; 30(2): 192.     CrossRef
  • Differences in surgical resection rate and risk of malignancy in thyroid cytopathology practice between Western and Asian countries: A systematic review and meta‐analysis
    Huy Gia Vuong, Hanh Thi Tuyet Ngo, Andrey Bychkov, Chan Kwon Jung, Trang Huyen Vu, Kim Bach Lu, Kennichi Kakudo, Tetsuo Kondo
    Cancer Cytopathology.2020; 128(4): 238.     CrossRef
  • Thyroid cancer among patients with thyroid nodules in Yemen: a three-year retrospective study in a tertiary center and a specialty clinic
    Butheinah A. Al-Sharafi, Jamila A. AlSanabani, Ibraheem M. Alboany, Amani M. Shamsher
    Thyroid Research.2020;[Epub]     CrossRef
  • Is Bethesda classification sufficient to predict thyroid cancer in endemic regions?
    Gamze ÇITLAK, Bahar CANBAY TORUN
    Journal of Surgery and Medicine.2020; 4(9): 794.     CrossRef
  • Preoperative diagnostic categories of fine needle aspiration cytology for histologically proven thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma: Analysis of cause of under- or misdiagnoses
    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
    PLOS ONE.2020; 15(11): e0241597.     CrossRef
  • Nuclear features of papillary thyroid carcinoma: Comparison of Core needle biopsy and thyroidectomy specimens
    Jae Yeon Seok, Jungsuk An, Hyun Yee Cho, Younghye Kim, Seung Yeon Ha
    Annals of Diagnostic Pathology.2018; 32: 35.     CrossRef
  • Clinical utility of EZH1 mutations in the diagnosis of follicular-patterned thyroid tumors
    Chan Kwon Jung, Yourha Kim, Sora Jeon, Kwanhoon Jo, Sohee Lee, Ja Seong Bae
    Human Pathology.2018; 81: 9.     CrossRef
  • The History of Korean Thyroid Pathology
    Soon Won Hong, Chan Kwon Jung
    International Journal of Thyroidology.2018; 11(1): 15.     CrossRef
  • Thyroid FNA cytology in Asian practice—Active surveillance for indeterminate thyroid nodules reduces overtreatment of thyroid carcinomas
    K. Kakudo, M. Higuchi, M. Hirokawa, S. Satoh, C. K. Jung, A. Bychkov
    Cytopathology.2017; 28(6): 455.     CrossRef
  • Thyroid Fine-Needle Aspiration Cytology Practice in Korea
    Yoon Jin Cha, Ju Yeon Pyo, SoonWon Hong, Jae Yeon Seok, Kyung-Ju Kim, Jee-Young Han, Jeong Mo Bae, Hyeong Ju Kwon, Yeejeong Kim, Kyueng-Whan Min, Soonae Oak, Sunhee Chang
    Journal of Pathology and Translational Medicine.2017; 51(6): 521.     CrossRef
  • Current Practices of Thyroid Fine-Needle Aspiration in Asia: A Missing Voice
    Andrey Bychkov, Kennichi Kakudo, SoonWon Hong
    Journal of Pathology and Translational Medicine.2017; 51(6): 517.     CrossRef
  • Current Status of Thyroid Fine-Needle Aspiration Practice in Thailand
    Somboon Keelawat, Samreung Rangdaeng, Supinda Koonmee, Tikamporn Jitpasutham, Andrey Bychkov
    Journal of Pathology and Translational Medicine.2017; 51(6): 565.     CrossRef
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
  • 10,445 View
  • 50 Download
  • 5 Crossref
PDF

Citations

Citations to this article as recorded by  
  • Digital Papillary Adenocarcinoma: Uncommon Malignancy of Sweat Glands - Two Rare Cases
    Neeti Goyal, Pawan Dhaman, Jasvinder Kaur Bhatia, Pragya Sharma, Prabha Shankar Mishra, Vikram Singh, Anvesh Rathore
    Journal of Marine Medical Society.2025; 27(1): 103.     CrossRef
  • Digital papillary adenocarcinoma: A case report of a rare malignant tumour with recommendations on management and follow-up
    Varanindu Mudduwa, Mohammad Goodarzi, Richard Chalmers, Haitham Khashaba
    International Journal of Surgery Case Reports.2025;[Epub]     CrossRef
  • Digital Papillary Carcinoma: A Literature Review of Epidemiology, Management Strategies, and Patient Outcomes
    William Liu, Rahul Nanda, David Zloty
    Dermatologic Surgery.2025;[Epub]     CrossRef
  • Digital papillary adenocarcinoma: A case report
    Betty A. Kasimo, Vivian Akello, James J. Yahaya
    Clinical Case Reports.2021;[Epub]     CrossRef
  • A rare case of a digital papillary carcinoma of the hand with secondary conservative management
    Rabeet Khan, Renu Irri, Effie Katsarma
    Journal of Surgical Case Reports.2020;[Epub]     CrossRef
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
  • 11,741 View
  • 56 Download
  • 1 Crossref
AbstractAbstract 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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  • 22 Download
AbstractAbstract 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.
Significance of Cyclin E, p53, E-cadherin, and beta-Catenin Expressions in Gastric Adenocarcinomas.
Long Pei Xuan, Mi Ja Lee, Chae Hong Suh
Korean J Pathol. 2004;38(4):213-220.
  • 2,068 View
  • 22 Download
AbstractAbstract PDF
BACKGROUND
Gastric cancer is reported to be one of the leading causes of mortality in Korea. Our aim was to evaluate the clinicopathologic usefulness of cyclin E, p53, E-cadherin and beta-catenin expressions in gastric adenocarcinomas.
METHODS
Immunohistochemical staining was performed on the 40 early gastric carcinoma (EGC) cases and 69 advanced gastric carcinoma (AGC) cases to examine the relationship with the clinicopathologic parameters.
RESULTS
Cyclin E and p53 expressions were significantly lower in the mucosal or submucosal invasion group compared with those in the muscle invasion and subserosal or serosal invasion groups. Cyclin E expression was significantly higher in the node-positive group compared with that in the node-negative group. The loss of beta-catenin expression was significantly higher in the node-negative group. p53 expression was significantly higher in the intestinal type group than that in the diffuse type group. Loss of E-cadherin expression was significantly higher in the diffuse type group. Cyclin E expression correlates with p53 expression.
CONCLUSIONS
The depth of invasion seems to correlate with cyclin E and p53 expressions. Lymph node metastasis may correlate with loss of beta-catenin expression.
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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AbstractAbstract 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
Adenocarcinoma with Yolk Sac Tumor of the Stomach: Case Report with Review of the Literature and an Immunohistochemical Study.
Ran Hong, Chae Hong Suh, Mi Ja Lee
Korean J Pathol. 2007;41(5):352-357.
  • 2,169 View
  • 16 Download
AbstractAbstract PDF
Gastric yolk sac tumors are extremely rare with only a few cases reported in the literature. Here, we present the case of a 50-year-old man with an adenocarcinoma and a yolk sac tumor of the stomach, without metastasis to the lymph nodes. The tumor was an early gastric carcinoma confined to the submucosa. Twelve months post-operation the patient was alive with no complications. The yolk sac tumor showed positive labeling for alpha-fetoprotein (AFP), alpha1-antitrypsin (alpha1-AT), cytokeratin (CK) and carcinoembryonic antigen (CEA), but was negative for human chorionic gonadotrophin (hCG), placental alkaline phosphatase (PLAP), epithelial membrane antigen (EMA) and p53. The adenocarcinoma was positive for alpha1-AT, CK, EMA, and CEA, but was negative for AFP, hCG, PLAP, and p53. These findings suggest that the yolk sac tumor and the adenocarcinoma components are closely related and may represent distinct phenotypes that arise from a common mucosal epithelial cell.
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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AbstractAbstract
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.
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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AbstractAbstract 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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AbstractAbstract 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.
Expression of Osteopontin, ZO-1 and E-cadherin in Adenoma and Adenocarcinoma of the Colon.
Yu Kyung Jeong, Mi Ja Lee, Sung Chul Lim, Keun Hong Kee, Ho Jong Jeon, Chae Hong Suh
Korean J Pathol. 2005;39(4):242-250.
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AbstractAbstract PDF
Background
: The expressions of osteopontin (OPN), zonula occludens-1 (ZO-1) and E-cadherin, known as cell adhesion-associated substances, were examined in adenoma and adenocarcinoma of the colon. The relationship of their expressions with clinicopathologic factors was examined to investigate the roles of these proteins in the development, invasion or metas- tasis of colon adenocarcinoma. Methods : The expressions of OPN, ZO-1, and E-cadherin were examined in 54 cases of adenoma and 67 cases of adenocarcinoma of the colon by immunohistochemical staining. Results : The expression of OPN in colon adenocarcinoma correlated with staging (p=0.012) and distant metastasis (p=0.021). The expression of ZO-1 was closely related with tumor cell differentiation (p<0.001), and the reduced expression of E-cadherin was associated with tumor cell differentiation (p=0.05) and lymph node metastasis (p<0.001). Co-expression of ZO-1 and E-cadherin was significantly associated with tumor cell differentiation, and the expressions of ZO-1 and E-cadherin were reduced or lost in all cases (5 cases) of poorly differentiated adenocarcinoma. Conclusions : Our data suggest that OPN is involved in the process of invasion and metastasis of colon adenocarcinoma, and ZO-1- and E-cadherin-mediated cell adhesion may play an important role in the differentiation of colon adenocarcinoma.
The Differential Expressions of the Epithelial-Mesenchymal Transition Regulator, Slug and the Cell Adhesion Molecule, E-cadherin in Colorectal Adenocarcinoma.
Ran Hong, Dong Yul Choi, Sung Chul Lim, Chae Hong Suh, Keun Hong Kee, Mi Ja Lee
Korean J Pathol. 2008;42(6):351-357.
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AbstractAbstract PDF
BACKGROUND
Slug is a member of the Snail family of transcription factors, and it plays a crucial role in the regulation of the epithelial-mesenchymal transition by suppression of several epithelial proteins and adhesion molecules, including E-cadherin. METHODS: The aim of the present study was to examine the significance between the expression of Slug in colorectal adenocarcinoma (CRA) specimens and the clinicopathological parameters of CRA, as determined by immunohistochemical analysis, and to determine the correlation between the Slug and E-cadherin expressions in non-neoplastic colorectal mucosa (n=45), primary CRA (n= 109) and metastatic CRA (n=17). A semiquantitative scoring system was applied based on the intensity and extent of the positive immunohistochemical staining. RESULTS: The expressions of Slug and E-cadherin were associated with the depth of tumor invasion (pT) (p=0.019, p=0.001, respectively), and these expressions showed a significant inverse correlation (p<0.001) each other. CONCLUSIONS: Our results demonstrated a positive role for Slug in the development of CRA, and Slug is a mediator of tumor invasion in CRA. In addition, an up-regulated Slug expression is significantly correlated with the loss of an E-cadherin expression, which suggests that Slug may play some role in the epithelial-mesenchymal transition (EMT) by down-regulating the E-cadherin expression.
Expressions of E2F4 and E2F2 Transcription Factors in Breast Carcinoma.
Eun Young Kim, Hyun Jin Jo, Mi Ja Lee
Korean J Pathol. 2005;39(5):301-306.
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AbstractAbstract PDF
BACKGROUND
The E2F family (E2F1 to E2F6) of transcription factors plays a key role in cell cycle progression. Some act as oncogenes and others act as tumor suppressor genes (TSG) in a tissue-specific manner. E2F4 may function as a TSG. However, the role of E2F4 in breast carcinogenesis remains controversial. Also the clinical impact of E2F2 expression on breast cancer remains unknown.
METHODS
Expressions of E2F4 and E2F2 were assessed immunohistochemically in 113 breast carcinomas and were compared with clinicopathological variables, expressions of G1/S checkpoint proteins (p16, cyclin D1 and Rb), and DNA ploidy to identify their possible role and to assess their prognostic value in breast cancer.
RESULTS
Expressions of E2F4 and E2F2 were detected in 48 cases (42.5%) and 66 cases (58.4%), respectively. Expressions of E2F4 and E2F2 were significantly correlated with large tumor size (p<0.001) and lymph node metastasis (p<0.001). There was no correlation between expressions of E2F4 or E2F2 and any other variables, including age, histologic grade, DNA ploidy and expressions of p16, cyclin D1 and Rb.
CONCLUSIONS
These results suggest that expressions of E2F4 and E2F2 are associated with growth and spread of breast cancer and indicate poor prognosis.
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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AbstractAbstract 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.
Case Report
Leukemic Infiltration of Acute Hybrid Leukemia with CD7 CD13+ and CD19+ Immunophenotype in the Lymph Node: A case report.
Mi Ja Lee, Ho Jong Jeok, Sang Woo Juhng
Korean J Pathol. 1994;28(2):191-199.
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AbstractAbstract PDF
Acute hybrid leukemia is an uncommon disease that demonstrates malignant transformation expressing lymphoid and myeloid cell lineage. We experienced a case of 25-year-old man with acute leukemia with unusual characteristics: unclassifiable morphology and undifferentiated cytochemistry by French-American-British (FAB) criteria. Microscopically, it disclosed monotonous tumor cell population in lymph node with vascular plugging and perivascular infiltration, and indian file appearance in capsule and surroun ng adipose tissue. Results of flow cytometry and immunohistochemical studies of frozen sections, cytospins, and formalin fixed lymphoid tissues disclosed hybrid form characterized by myeloid and lymphoid cell lineage. The immunophenotype analysis showed both anti-T cell, anti-B cell and anti-myeloid cell monoclonal antibody reactivity; blast cells were consistently CD7+(94.6%), CD13+(97.1%), and CD19+(85.22%). The normal hematopoietic cells were almost replaced by tumor cells in PB and bone marrow. In preparation of cytospin of peripheral blood(PB) cells separated by a Ficoll-hypaque gradients, blast cells were negative for Sudan black B, myeloperoxidase, periodic acid Schiff, and nonspecific esterase.
Original Article
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
J Pathol Transl Med. 1995;6(2):106-115.
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AbstractAbstract 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.
Case Reports
Effusion Cytology of Ki - 1 Positive Anaplastic Large Cell Lymphoma: A Case Report.
Mi Sook Lee, Mi Ja Lee, Yu Kyung Jeong, Sung Chul Lim, Keun Hong Kee, Ho Jong Jeon
J Pathol Transl Med. 1995;6(2):163-168.
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AbstractAbstract PDF
Ki-1 positive anaplastic large cell lymphoma is a newly described high-grade lymphoma and is defined by histopathological and immunologic criteria. We experienced a case of systemically involving Ki-1 positive anaplastic large cell lymphoma in a 44 year-old female which initially manifested as pleural effusion. Abdominopelvic CT scan showed the evidence of marked lymphadenopathy in retroperitoneal and both external and inguinal lymph nodes. On cytologic examination of pleural fluid tumor cells revealed pleomorphic large isolated cells with prominent nucleoli and abundant cytoplasms. The nuclei were large with irregular profiles including some deep invaginations. Also. occasional multilobed/multinucleated and binucleated nuclei were seen. Immunohistochemical examination was performed to differentiate from the undifferentiated adenocarcinoma. Hodgkin's disease, non-Hodgkin's lymphoma and malignant histiocytosis. The neoplastic cells were positive for leukocyte common antigen. CD3 CD30(ki-1) but negative for cytokeratin. epithelial membrane antigen. and CD15. A histologic diagnosis of Ki-1 positive anaplastic lymphoma was made by biopsies of the inguinal lymph node, polypoid lesion of the stomach and cecum.
Cytology of Anaplastic Thyroid Carcinoma with Varied Histologic Patterns Arising in Preexisting Goiter: Report of A Cese.
Mi Ja Lee, Mi Sook Lee, You Kyung Jeong, Sung Chul Lim, Keun Hong Kee, Ho Jong Jeon
J Pathol Transl Med. 1995;6(2):187-192.
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AbstractAbstract PDF
Anaplastic carcinoma of the thyroid(ACT0 is a rare subtype of thyroid neoplasm. This tumor represents approximately 5-10% of all thyroid malignancies and has poor prognosis. ACT often arises in a long-standing thyroid nodule and has been documented to be associated with a variety of more with a variety of more well-differentiated thyroid carcinomas. We experienced a case of anaplastic thyroid carcinoma who had had about a year history of thyroid goiter. The patients had been injected with sclerosing agents in treatment of preexisting goiter. The ACT in this case had varied cytologic and histologic appearances pleomorphic, giant cells, spindle and squamoid. Immunohistochemically, strong cytoplasmic positivity for cytokeratin was seen in all kinds of tumor cells. Ultrastructurally. the evidences of epithelial differentiation were seen such as intercellular junctions and tonofibrils.
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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AbstractAbstract 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.
Original Article
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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AbstractAbstract 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.
Case Report
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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AbstractAbstract 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 Articles
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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AbstractAbstract 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.
Significance of p53, cyclin D1 and c-myc Expressions in Thyroid Tumors.
Zhuhu Li, Ho Jong Jeon, Mi Ja Lee
Korean J Pathol. 2004;38(1):29-34.
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AbstractAbstract PDF
BACKGROUND
The G1/S phase proteins of the cell cycle play critical roles in tumorigenesis and tumor progression. Our aim was to investigate the significance of p53, cyclin D1 and c-myc expressions in thyroid tumors.
METHODS
The expressions of these proteins were examined in 217 cases of thyroid tumors and tissues using immunohistochemistry. The results were correlated with lymph node metastasis.
RESULTS
p53 expression was seen in 75.5, 47.5, 66.7, and 50% of papillary carcinomas (PC), follicular carcinomas (FC), undifferentiated carcinomas (UC) and follicular adenomas (FA), respectively. There was a significant difference between these expressions in these tumors and the results in nodular hyperplasia (NH) and normal tissues. Cyclin D1 expression was noted in 80.0, 68.4, 66.7, 61.1 and 79.5% of PC, FC, UC, FA and NH, respectively. c-myc expression was seen in 80.0, 94.2, 66.7, 66.7 and 52.3% of PC, FC, UC, FA and NH, respectively. There was a significant association between the expressions in these tumors and the results in normal tissues. The expressions of p53, cyclin D1 and c-myc were not correlated with lymph node metastasis.
CONCLUSIONS
These findings suggest the expressions of p53, cyclin D1 and c-myc may act in the early stage, and participates in tumorigenesis and promoting cell growth.
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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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.

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