Prognostic relevance of p53 and bcl-2 immunoreactivity for early invasive pT1/pT2 gastric carcinomas: indicators for limited gastric resections?

Abstract

Background: Laparoscopic or endoscopic limited resection is intended to be an additional therapeutic option for the treatment of early gastric cancer. However, tumorbiologic markers to predict the outcome for patients after limited resections are missing. This study therefore investigated the prognostic relevance of p53 and bcl-2 immunoreactivity as well as the percentage of apoptotic tumor cells in early invasive pT1/pT2 tumors managed with standard operations for gastric adenocarcinoma.

Methods: Histologic slides of 65 pT1/pT2 gastric carcinomas were investigated for bcl-2 and p53 immunoreactivity. For 35 patients, DNA fragmentation of tumor cell nuclei was determined by the terminal uridine 5'-triphosphate (UTP) nick end-labeling (TUNEL) method. Follow-up evaluation of the patients was prospectively documented for 53.4 +/- 4.1 months.

Results: Findings showed that bcl-2 immunoreactivity was associated with tumors of the intestinal type according to Lauren s classification (p = 0.042), and that p53 immunoreactivity was increased in more invasive tumors (pT1 vs pT2 tumors; p = 0.047). Mean survival time was significantly longer for patients with bcl-2-negative tumors (74.3 +/- 6.8 months) than for patients with bcl-2-positive tumors (50.8 +/- 7.6 months; p = 0.024). The percentage of apoptotic tumor cell nuclei did not have prognostic relevance in the population studied and was not associated with several histopathologic parameters or bcl-2 and p53 immunoreactivity. Subgroup analysis indicated that the survival of patients with differentiated G2 and bcl-2-negative/p53-negative tumors was significantly longer (82 +/- 6 months) than the survival of patients with G2 bcl-2- and/or p53-positive tumors (41.8 +/- 12.5 months; p = 0.005), with independent prognostic relevance determined by multivariate analysis (p = 0.024).

Conclusion: The data reported indicate that the analysis of bcl-2 and p53 immunoreactivity seems to have prognostic implications for early invasive (pT1/pT2) gastric adenocarcinomas and may subclassify patients for minimally invasive laparoscopic or endoscopic gastric resections.