Gene amplification and proliferative kinetics in relation to prognosis of patients with gastric carcinoma.

Abstract

The differences in survival of gastric carcinoma patients who have identical clinical or pathologic stages prompted the authors to investigate the prognostic significance of biologic features that are known to affect the clinical aggressiveness of other tumor types. One hundred twenty-four tumor samples from patients who had received radical or palliative surgery were analyzed for c-myc, c-K-ras, hst, and c-erb B-2 gene amplification by means of the Southern blot technique. Of these tumors, 70 were also examined for cell kinetics by means of the thymidine labeling index (TLI). The analysis of associations between gene amplification and the anatomicopathologic variables (TNM classification, site of tumor, and histology) showed that amplification represents a late event in the natural history of gastric carcinoma. Gene amplification showed a slight, statistically insignificant, negative impact on overall survival (OS) (P = 0.09). Amplification of c-erb B-2 correlated in a statistically significant way with reduced OS (P = 0.03). Cox multiple regression analysis revealed that neither c-erb B-2 amplification nor TLI had prognostic significance in relation to OS. These data indicate that amplification of the examined oncogenes did not reveal a new independent prognostic factor for patients with gastric carcinoma. However, the authors' results did show a strong correlation between gene amplification and tumor progression, which warrants further study involving larger series of patients. At the same time, the TLI results underlined the need to identify the most suitable biologic material for use in the estimation of proliferative indexes in gastric carcinoma.