The clinicopathological features of gastric carcinomas with microsatellite instability may be mediated by mutations of different "target genes" - A study of the TGF beta RII, IGFII R, and BAX genes

• Type: Article in International Scientific Journal
• Date: 1998

Authors

Oliveira, C (Author) Other; Seruca, R (Author) Other; Seixas, M (Author) Other; Sobrinho Simoes, M (Author) FMUP

Journal

Title: American Journal of Pathology

Vol. 153

Pages: 1211-1219

ISSN: 0002-9440

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 118 Citations

Scopus - 129 Citations

Other information

Authenticus ID: P-001-6YB

DOI: 10.1016/s0002-9440(10)65665-9

Abstract (EN): Gastric carcinomas with DNA replication errors (RER phenotype) display a particular clinicopathologic profile and carry a putative favorable prognosis. The RER phenotype has been identified as microsatellite instability in noncoding regions, as well as in repeat sequences within exons of several "target genes": TGF beta RII, IGFII R, and BAX. In an attempt to fmd out whether the RER status is a significant prognostic factor in gastric carcinoma in a multivariate analysis and whether the clinicopathological features of the RER+ tumors are associated with mutations in the "target genes," we evaluated a series of 152 cases of sporadic gastric carcinoma. Five or six microsatellite loci and/or BAT 26, a poly(A) tract, were analyzed in each case using polymerase chain reaction and electrophoresis. Thirty-five cases (23.0%) were RER+, The RER phenotype was closely associated with a low pTNM stage and carried a significantly better prognosis. The repeat sequences of the target genes were screened for mutations in 28 RER+ and 13 RER-tumors. Mutations in TGF beta RII occurred in 67.9% of the RER+ tumors and were significantly associated with the glandular histotype, IGFII R and BAX mutations occurred, respectively, in 25.0% and 32.1% of the cases; there was a trend toward an association between mutations in these genes and decreased nodal metastization and wall invasiveness, respectively. We conclude that the RER status is a significant prognostic indicator in gastric carcinoma and that such prognostic influence may be mediated by mutations in TGF beta RII, IGFII R, and BAX genes.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9