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Tumour suppressor gene expression correlates with gastric cancer prognosis
Author(s) -
Lee Hye Seung,
Lee Hyeon Kook,
Kim Hee Sung,
Yang HanKwang,
Kim Woo Ho
Publication year - 2003
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1288
Subject(s) - pten , cancer , cancer research , cdh1 , carcinogenesis , biology , fhit , tumor suppressor gene , loss of heterozygosity , suppressor , carcinoma , cd44 , pathology , gene , medicine , cadherin , apoptosis , cell , genetics , pi3k/akt/mtor pathway , allele
The loss of tumour suppressor genes (TSGs) is a key event in many human cancers, including gastric carcinoma. Many TSG candidates have been studied, but their roles in gastric carcinogenesis remain unclear. To clarify the clinical significance of TSG expression in gastric carcinoma, the expression of various TSG candidates (p53, E‐cadherin, FHIT, smad4, rb, VHL, PTEN, MGMT, p16, and KAI1), as well as other proteins (bcl‐2, MUC1, MUC2, MUC5AC, MUC6, CEA, CD44, β‐catenin, C‐erbB2, and cyclin B2), was evaluated immunohistochemically in 329 consecutive gastric carcinomas using the tissue array method. The overexpression of p53 and MUC1 ( p < 0.01) and the loss of expression of smad4 ( p = 0.04), FHIT ( p = 0.03), MGMT ( p = 0.01), E‐cadherin, KAI1, and PTEN ( p < 0.01) were found to be significantly associated with poor gastric carcinoma prognosis. Seven out of eight survival‐associated proteins were found to be protein products of TSGs. The gastric carcinomas were divided into five groups according to the grade of alteration in TSG expression. No TSG expression loss was found in 32 cases (TSG1). One TSG loss was found in 47 cases (TSG2), two in 67 cases (TSG3), three or four in 64 cases (TSG4), and five, six, or seven in 38 cases (TSG5). The grade of TSG expression was confirmed to be significantly associated with WHO classification ( p = 0.04), pTNM stage, lymphatic invasion, and patient survival ( p < 0.01 for the latter three). By multivariate analysis, the grade of TSG expression was found to be significantly and independently associated with patient survival ( p < 0.01). In conclusion, the findings of this study suggest that the cumulative loss of TSG expression in gastric carcinoma is important in determining patient survival. Copyright © 2003 John Wiley & Sons, Ltd.