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      • Class III &bgr;-Tubulin Shows Unique Expression Patterns in a Variety of Neoplastic and Non-neoplastic Lymphoproliferative Disorders

        Yoon, Sun Och,Kim, Wook Youn,Go, Heounjeong,Paik, Jin Ho,Kim, Ji Eun,Kim, Young A.,Huh, Joo R.,Jeon, Yoon Kyung,Kim, Chul-Woo Lippincott Williams Wilkins, Inc. 2010 The American journal of surgical pathology Vol.34 No.5

        Class III &bgr;-tubulin (TUBB3) expression in carcinoma is associated with resistance to tubulin-binding chemotherapeutic agents. Recently, follicular dendritic cells (FDCs) were reported to express TUBB3 under physiologic conditions. We investigated TUBB3 expression in a wide range of lymphoproliferative disorders using immunohistochemistry. Dual immunostaining for Bcl-6 and TUBB3 revealed that some germinal center B cells also express TUBB3 in addition to FDCs. In Hodgkin lymphomas (HLs), 47.1% (40/85) expressed TUBB3 in the tumor cells with an all-or-none pattern. TUBB3 expression in HL was more common in mixed cellularity type than nodular sclerosis type (P=0.032). Among non-HLs, 79.3% (23/29) of anaplastic large cell lymphoma (ALCL), 8% (2/25) of extranodal natural killer/T-cell lymphoma, and 75% (21/28) of Burkitt lymphoma showed TUBB3 expression with an all-or-none pattern. Of diffuse large B-cell lymphoma, 15.2% (32/210) expressed TUBB3 in a heterogeneous pattern. In ALCL, TUBB3 expression was more common in systemic ALCL than in primary cutaneous ALCL (P=0.046). Diffuse large B-cell lymphomas with a germinal center B-like subgroup exhibited TUBB3 expression more frequently than non−GCB-like subgroup (P=0.01). Otherwise, none of the 18 angioimmunoblastic T-cell lymphomas; 18 peripheral T-cell lymphomas, not otherwise specified; 12 follicular lymphomas; 62 marginal zone lymphomas; 7 mantle cell lymphomas; 8 small lymphocytic lymphomas; or 2 FDC sarcomas expressed TUBB3. In angioimmunoblastic T-cell lymphoma and Castleman disease, TUBB3 was positive in immunoblasts corresponding to Epstein-Barr virus-infected or Kaposi sarcoma herpes virus-infected cells. A variety of neoplastic and non-neoplastic lymphoproliferative disorders exhibited characteristic TUBB3 expression patterns; these results suggest potential for diagnostic utility, some insight into the pathobiology of TUBB3 expression, and potential therapeutic implications.

      • Differential protein immunoexpression profiles in appendiceal mucinous neoplasms: a special reference to classification and predictive factors

        Yoon, Sun Och,Kim, Baek-hui,Lee, Hye Seung,Kang, Gyeong Hoon,Kim, Woo Ho,Kim, Young A,Kim, Je Eun,Chang, Mee Soo Springer Science and Business Media LLC 2009 Modern pathology Vol.22 No.8

        <P>Appendiceal mucinous neoplasms have been the focus of considerable debate in recent years. We histologically classified 70 appendiceal mucinous neoplasms into three categories: 32 mucinous adenoma, 23 mucinous neoplasm of uncertain malignant potential, and 15 mucinous adenocarcinomas. Immunohistochemistry was performed for 24 proteins in different functional categories, specifically, oncogenic proteins (bcl-2, beta-catenin, CEA, C-erbB2, c-kit, Cox-2, Cyclin D1, EGFR, Ki-67, NF-kappaB, VEGF), tumor suppressors (E-cadherin, FHIT, hMLH1, p53, p63, smad4), cell-cycle regulators (p21, p27, p16), and mucin proteins (MUC1, MUC2, MUC5AC, MUC6). Our data showed that 9 out of the 24 proteins were more frequently altered in the mucinous adenocarcinoma group than in the mucinous adenoma group (P<0.05), including beta-catenin (13% in mucinous adenoma vs 60% in mucinous adenocarcinoma), CyclinD1 (44 vs 87%), Ki-67 (high labeling index: 31 vs 67%), NF-kappaB (19 vs 60%), VEGF (16 vs 87%), E-cadherin (0 vs 47%), p53 (6 vs 40%), MUC2 (9 vs 67%), and MUC5AC (3 vs 40%). The distinct immunoexpression profile of mucinous neoplasm of uncertain malignant potential was placed between those of mucinous adenoma and mucinous adenocarcinoma (P<0.05). Moreover, the mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma categories displayed differences in terms of the number of altered markers among the nine proteins (P<0.05; mean 1.4 vs 2.6 vs 5.5, respectively). In mucinous adenocarcinoma, the p53 status was related to disease-free survival and overall survival of patients (P<0.05, both). NF-kappaB status and the number of altered protein markers made statistically marginal impacts on disease-free survival; also beta-catenin loss, on overall survival of patients. In conclusion, protein immunoexpression profiles may facilitate the classification of appendiceal mucinous neoplasms. In our study, the three tumor categories of mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma exhibited distinct immunoexpression profiles. Five and more altered protein markers, p53 overexpression, NF-kappaB positivity, and beta-catenin loss were predictive factors of adverse clinical outcomes in appendiceal mucinous adenocarcinomas.</P>

      • KCI등재

        Cytologic Features of Giant Cell Ependymoma: A Case Report and Review of the Literature

        Koh, Myoung Ju,Yoon, Sun Och,Jeon, Hyae Min,Jeong, Hyeon Joo,Hong, Soon Won,Kim, Se Hoon 대한병리학회 2012 Journal of Pathology and Translational Medicine Vol.46 No.5

        <P>Here, we present a case of anaplastic giant cell ependymoma (GCE) occurring in a 15-year-old woman. Squash smear slides for intraoperative frozen section diagnosis revealed oval to round cell clusters with a papillary structure in a fibrillary background. This was occasionally accompanied by the presence of bizarre pleomorphic giant cells with hyperchromatic nuclei and prominent intranuclear inclusions. These intranuclear inclusions were a key clue to diagnosis of ependymoma. Histologic analysis revealed features of a high-grade tumor with perivascular pseudorosettes and bizarre pleomorphic giant cells, which established the diagnosis of GCE. We performed a review of literatures about the cytologic features of GCE, including our case, thus proposing that intraoperative frozen diagnosis of GCE would be established by squash smear preparations featuring the mitosis and necrosis, as well as the high cellularity, and the presence of giant cells showing hyperchromatic nuclei with eosinophilic cytoplasm and intranuclear inclusions/pseudoinclusions.</P>

      • SCIESCOPUS

        Thioredoxin and thioredoxin-interacting protein as prognostic markers for gastric cancer recurrence.

        Lim, Jae Yun,Yoon, Sun Och,Hong, Soon Won,Kim, Jong Won,Choi, Seung Ho,Cho, Jae Yong WJG Press 2012 WORLD JOURNAL OF GASTROENTEROLOGY Vol.18 No.39

        <P>To evaluate the potential of thioredoxin (TXN) and thioredoxin-interacting protein (TXNIP) expression as biomarkers for predicting gastric cancer recurrence.</P>

      • SCIESCOPUS

        Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer.

        Lim, Jae Yun,Yoon, Sun Och,Seol, So Young,Hong, Soon Won,Kim, Jong Won,Choi, Seung Ho,Cho, Jae Yong WJG Press 2012 WORLD JOURNAL OF GASTROENTEROLOGY Vol.18 No.30

        <P>To investigate M2 isoform of pyruvate kinase (PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.</P>

      • SCISCIESCOPUS
      • Leptin, MUC2 and mTOR in Appendiceal Mucinous Neoplasms

        Chang, Mee Soo,Byeon, Sun-ju,Yoon, Sun Och,Kim, Baek-hui,Lee, Hye Seung,Kang, Gyeong Hoon,Kim, Woo Ho,Park, Kyu Joo S. Karger AG 2012 Pathobiology Vol.79 No.1

        <P><I>Objective:</I> Leptin contributes to mucin production in colonic epithelium and regulates carcinogenesis via various signalling pathways. We evaluated the proteins involved in mucin-producing carcinogenesis and putative targets for molecular therapy in appendiceal mucinous neoplasms. <I>Methods:</I> Immunohistochemistry and fluorescence in situ hybridization were performed in 22 cases of appendiceal mucinous adenoma, 20 mucinous neoplasms of uncertain malignant potential and 14 mucinous adenocarcinomas. <I>Results:</I> Leptin, MUC2, MUC5AC, mTOR and ERK were more frequently immunopositive in mucinous adenocarcinomas compared with mucinous adenomas or mucinous neoplasms of uncertain malignant potential (p < 0.05). STAT3 revealed immunopositivity in 82% of tumours, regardless of tumour category. MUC2 immunopositivity was associated with pseudomyxoma peritonei (p < 0.05). None of the tumours exhibited c-kitimmunoexpression, amplification of <I>Her2</I> or <I>EGFR,</I> or translocation of <I>ALK</I>. The mTOR-immunopositive group of patients had a lower rate of disease-free survival compared with the mTOR-immunonegative group (p < 0.05). <I>Conclusions:</I> Leptin may collaborate with MUC2 and MUC5AC in mucin-producing carcinogenesis in an mTOR-, STAT3- and ERK-dependent manner. STAT3 may be activated early during tumorigenesis. <I>MUC2</I> and <I>mTOR</I> (but not c<I>-kit</I>, <I>Her2</I>, <I>EGFR </I>and <I>ALK</I>) may represent targets for molecular therapy in pseudomyxoma peritonei and appendiceal mucinous adenocarcinoma, respectively.</P><P>Copyright © 2012 S. Karger AG, Basel</P>

      • Cytotoxic mycosis fungoides with clinical features of hypopigmentation and poikiloderma at the same time

        ( Shinwon Hwang ),( Jaemin Kim ),( Sun Och Yoon ),( Sang Ho Oh ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.1

        There are many variants type of mycosis fungoides (MF), including folliculotropic MF, hypopigmented MF and so on. Those variant types are usually rarely presented. Also, pathologically cytotoxic MF which expresses a CD8+ phenotype rather than CD4 is a rare clinical variant. We reported a case of cytotoxic MF which showed clinical features of hypopigmentation and poikiloderma simultaneously. A 51 year-old woman presented with about 20cm sized erythematous telangiectatic atrophic patch and several ill-defined hypopigmented patches on both buttock and thigh. She reported that she has had erythematous lesion on left buttock for more than 20 years and she noticed hypopigmented lesions from several months before. There were atypical infiltration in the epidermis and dermis with linear accumulation of atypical lymphocyte along the basement membrane on center of both pokiloderma and hypopigmented lesion. Immunohistochemistry study showed most infiltrated cells were CD3 positive, CD30 negative with CD8 dominant pattern. Positive clonality of T cell receptor was observed in gene rearrangement study. Therefore, she was diagnosed as cytotoxic MF due to CD8+ dominant infiltration with epidermotrophism. MF variant is usually rare presentation of cutaneous MF. Even in our case, disease showed that cytotoxic MF with hypopigmentation and poikilodermic features rare presentations of MF. Therefore, we report a unique MF case showed all of these features.

      • The implications of TrkA and MET aberrations in de novo salivary duct carcinoma

        Ryu, Hyang Joo,Koh, Yoon Woo,Yoon, Sun Och Elsevier 2018 Human pathology Vol.81 No.-

        <P><B>Summary</B></P> <P>Salivary duct carcinoma (SDC) is an aggressive carcinoma with poor prognosis. Although anti-HER2 therapy is a potential treatment option for HER2-positive SDC, other potential therapeutic targets are not known, in particular for HER2-negative cases. In this study, the recently identified receptors tyrosine kinases MET and tropomyosin-receptor kinase (Trk) were investigated as potential therapeutic targets. A total of 28 consecutive, surgically resected, de novo SDC cases were selected after evaluating histology and immunohistochemical expression of androgen receptor. Immunohistochemical expression of c-erb2, TrkA, TrkB, TrkC, and c-MET was analyzed, and the genetic status of the <I>HER2</I> and <I>MET</I> genes was investigated through dual-color silver in situ hybridization. High expression of c-MET or Trk was defined as that above the median value. Among the 28 SDC cases, 64.3% (18/28) were HER2-positive. c-MET expression varied, with a median H-score of 65 (range, 0 to 200). Copy number gain and amplification of <I>MET</I> were noted in 57.1% (16/28) and 10.7% (3/28) of cases, respectively. TrkA was variably expressed, with a median H-score of 100 (range, 0 to250). High TrkA expression was significantly related to an inferior overall survival rate in HER2-negative SDC. High expression of TrkA and c-MET and <I>MET</I> copy number gain/amplification were frequent events in SDC, and high expression of TrkA revealed the tendency to be related to poor prognosis in HER2-negative SDC. TrkA and MET may be possible therapeutic targets in SDC, especially in HER2-negative SDC.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Salivary duct carcinoma (SDC) is an aggressive carcinoma </LI> <LI> High expression of TrkA and c-MET and <I>MET</I> gene copy number gain/amplification are frequent events in SDC. </LI> <LI> High expression of TrkA reveals the tendency to be related to poor prognosis in HER2-negative de novo SDC. </LI> <LI> TrkA and MET may be possible targets in SDC and in HER2-negative SDC. </LI> </UL> </P>

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