Clinical Significance of CD99 Down-Regulation in Gastric Adenocarcinoma

Lee, Jung Hyun; Kim, Seok-Hyung; Wang, Lihui; Choi, Yoon–La; Kim, Young Chul; Kim, Jin Hee; Park, Tae Sung; Hong, Yun–Chul; Shin, Young Kee

doi:10.1158/1078-0432.ccr-06-1785

Cited by 30 publications

(30 citation statements)

References 32 publications

(24 reference statements)

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“…This finding further underscore the non-specific diagnostic nature of CD99 as reported in several tumor studies and the collective use of complementary markers [1,4,28,29,30]. However, the recent finding of the role of CD99 in the biological evaluation of certain tumors indicates that further studies are needed [31]. The keratin expression in the rhabdomyosarcoma case was negated by the positive detection of multiple skeletal muscle markers [30,32].…”

Section: Discussionmentioning

confidence: 82%

Molecular and phenotypic analysis of poorly differentiated sinonasal neoplasms: an integrated approach for early diagnosis and classification

et al. 2009

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Accurate early diagnosis of poorly differentiated tumors of the sinonasal and skull-base sites is critical to modern multimodality management of patients with these tumors. A combined phenotypic and sequential biomarkers approach of a large retrospective cohort of these tumors led to the reclassification of some cases and the confirmation of uncertain diagnoses in others. An integrated algorithm of selected markers and phenotypic features for biopsy-based diagnosis of these tumors is presented and discussed. Primary poorly differentiated (small round and non-small) sinonasal neoplasms comprise histogenetically and biologically diverse entities with overlapping morphologic features. Because of the limited initial biopsy tissue materials, differential diagnostic difficulties may arise and complicate timely management of some cases. We employed immunohistochemical and molecular marker analyses in a large cohort of these tumors to optimize their early diagnosis and classification. Fifty-two tumors of the skull base and sinonasal regions and, for comparison, 19 poorly differentiated neoplasms of other head and neck sites were analyzed by a panel of immunohistochemical markers including those of epithelial, mesenchymal, melanocytic, and neuroectodermal origin using tissue microarray. RT-PCR analysis of mRNA for EWS-FLI1 and PAX-FKHR fusion transcripts and the hASH1 gene was performed on 24 of the 52 sinonasal tumors and the 19 tumors of other sites for comparison. The immunohistochemical results substantiated the phenotypic assessment and the initial diagnosis in 49 of the 52 tumors. In four instances the integrated markers and phenotypic analyses led to reclassification of three tumors and confirmed the histogenesis of a mesenchymal tumor with aberrant cytokeratin expression. Molecular analysis of the EWS-FLI1 fusion gene transcript revealed four (9.3%) of the 43 tumors to be positive; all were Ewing’s sarcomas. The hASH1 gene transcript was identified in 10 (23.8%) of 42 tumors: three of six neuroblastomas, all four neuroendocrine carcinomas, and one each in sinonasal undifferentiated carcinoma, rhabdomyosarcoma, and melanoma. The PAX-FKHR fusion transcript was not detected in any tumors. We conclude that 1) an integrated morphologic and biomarker algorithm may better optimize the early diagnosis of poorly differentiated sinonasal and skull-base tumors; 2) molecular analysis may assist in future biological stratification of certain classes of these tumors; and 3) the hASH1 gene transcript is a nonspecific marker for the diagnosis of neuroblastoma.

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Section: Discussionmentioning

confidence: 82%

Molecular and phenotypic analysis of poorly differentiated sinonasal neoplasms: an integrated approach for early diagnosis and classification

et al. 2009

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“…The immunoreactivity for CD99 in Merkel cell carcinoma should be taken into consideration when diVerential diagnosis with other small round blue cell tumors is considered (Sur et al 2007). Lee et al (2007) reported that the expression of CD99 was signiWcantly decreased in the gastric carcinoma and intestinal metaplasia samples compared with normal gastric epithelial. However, so far CD99 expression status in TCC has been rarely reported.…”

Section: Discussionmentioning

confidence: 99%

“…Increased or decreased expression of CD99 has been suggested to act as a marker of various kinds of tumors, including Ewing's sarcoma/primitive neuroectodermal tumors (Fong et al 2008), anaplastic large cell lymphoma (Buxton et al 2009), lymphoblastic lymphoma/leukemia (Kang and Dunphy 2006), rhabdomyosarcoma (Folpe et al 2002;Euscher et al 2008), ovarian tumors (Choi et al 2000), and stomach cancer Lee et al 2007). However, the clinical implication of CD99 in epithelial tumors including transitional cell carcinoma of urinary bladder has been rarely studied.…”

Section: Introductionmentioning

confidence: 99%

Protein expression and gene promoter hypermethylation of CD99 in transitional cell carcinoma of urinary bladder

Xuan

Kim

Lin

2010

J Cancer Res Clin Oncol

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“…CD9 is a cell surface protein that has been implicated in a number of cellular processes including cutaneous wound healing 23 ; CD9 was down-regulated in migrating epidermis, and re-elevated to basal level when re-epithelialization was completed, supporting that low level of CD9 is required for normal wound healing 23 . Although its function is not fully understood, CD99 is thought to be involved in a number of cellular events such as cell-cell adhesion and maintenance of cellular morphology, and altered expression levels of CD99 have been found in several types of cancer 24 . We found that CD99 was decreased by 45% (i.e., ratio of treated/untreated cells being 0.55) as a result of NNN exposure.…”

Section: Resultsmentioning

confidence: 99%

Quantitative Proteomic Analysis Revealed N′-Nitrosonornicotine-induced Down-regulation of Nonmuscle Myosin II and Reduced Cell Migration in Cultured Human Skin Fibroblast Cells

Prins

Wang

2013

J. Proteome Res.

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The association of tobacco smoke with decreased cell motility and wound healing is well documented; however, the cellular mechanisms and specific toxic tobacco constituents responsible for this effect are not well understood. Tobacco-specific N-nitrosamines (TSNAs) are among the most important classes of carcinogens found in tobacco products. The TSNA N′-nitrosonornicotine (NNN) is present at relatively high levels in tobacco and its smoke, as well as second- and third-hand smoke. To investigate the cellular pathways that are perturbed upon NNN exposure, we employed a quantitative proteomic approach, utilizing stable isotope labeling by amino acids in cell culture and mass spectrometry, to assess the NNN-induced alteration of protein expression in GM00637 human skin fibroblast cells. With this approach, we were able to quantify 2599 proteins, 191 of which displayed significantly changed expression following NNN exposure. One of the main findings from our proteomic analysis was the down-regulation of six different subunits of myosin, particularly non-muscle myosin II heavy chain, isoforms A, B, and C. In addition, we found the altered expression of several extracellular matrix proteins and proteins involved in cellular adhesion. Together, our quantitative proteomic results suggested that NNN exposure may interfere with fibroblast motility. An in vitro scratch wound assay results supported that NNN exposure reduced the ability of dermal fibroblast to migrate into the scratched area. The results from the present study offered novel insights into the cellular mechanisms of NNN toxicity and identified NNN as a specific tobacco constituent that contributes to decreased fibroblast migration.

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Clinical Significance of CD99 Down-Regulation in Gastric Adenocarcinoma

Cited by 30 publications

References 32 publications

Molecular and phenotypic analysis of poorly differentiated sinonasal neoplasms: an integrated approach for early diagnosis and classification

Molecular and phenotypic analysis of poorly differentiated sinonasal neoplasms: an integrated approach for early diagnosis and classification

Protein expression and gene promoter hypermethylation of CD99 in transitional cell carcinoma of urinary bladder

Quantitative Proteomic Analysis Revealed N′-Nitrosonornicotine-induced Down-regulation of Nonmuscle Myosin II and Reduced Cell Migration in Cultured Human Skin Fibroblast Cells

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