Helicobacter pylori and Molecular Markers as Prognostic Indicators for Gastric Cancer in Korea

Abstract

Background: The prognosis of H. pylori infection-negative gastric cancer (HPIN-GC) has been rarely investigated. Applying a strict definition of H. pylori status, the prognosis and molecular prognostic markers in HPIN-GC were evaluated.

Methods: A combination of multiple methods was carried out to strictly evaluate H. pylori infection in gastric cancer (GC) patients between June 2003 and October 2012 at Seoul National University Bundang Hospital. H. pylori infection was defined as negative if histology, a rapid urease test, culturing, serology and history of H. pylori eradication were all negative. Patients with severe gastric atrophy by the serum pepsinogen test or histology were assumed to have had a previous H. pylori infection. Epstein-Barr virus (EBV) in situ hybridization, PCR-based microsatellite instability (MSI) testing, and p53 immunohistochemistry were performed.

Results: Compared to 509 H. pylori infection-positive gastric cancer (HPIN-PC) patients, 24 HPIN-GC patients showed a significantly higher frequency of cardia location (P=0.013), and the depth of invasion in HPIN-GC was more advanced, although there was no statistical significance (pT3-pT4, 37.5% for HPIN-GC vs. 28.5% for HPIP-GC, P=0.341). In multivariate analysis, depth of invasion and lymph node metastasis were identified as the most important prognostic factors for relapse-free survival and overall survival (P<0.001). However, the status of H. pylori infection was not an independent prognostic factor for relapse-free survival and overall survival. The positivity of EBV in both groups was low, and the survivals according to MSI and p53 status in HPIN-GC patients were not significantly different.

Conclusions: The status of H. pylori infection was not a prognostic factor for survival in GC patients when applying the strict definition of H. pylori infection. The prognostic implication of MSI and p53 on survival in HPIN-GC patients was not clear.

Keywords: Gastric cancer; Helicobacter pylori; Microsatellite instability; Prognosis; p53.

Fig. 1.

Flow chart applying the strict definition of H. pylori infection for the comparison of clinicopathologic and molecular characteristics between H. pylori-infection positive and negative gastric cancer patients. ^aHistology, rapid urease test, and culture for H. pylori. ^bPatients who had undergone endoscopic resection or palliative surgery were excluded in the pathologic evaluation.

Fig. 2.

Effects of H. pylori status and molecular markers on overall survival. Overall survival in 533 gastric cancer patients according to (A) T stage, (B) N stage, (C) Lauren classification, (D) tumor size, and (E) H. pylori status. Overall survival in 24 H. pylori-infection negative gastric cancer patients according to (F) microsatellite instability (MSI) and (G) p53 expression.

Fig. 2.

Effects of H. pylori status and molecular markers on overall survival. Overall survival in 533 gastric cancer patients according to (A) T stage, (B) N stage, (C) Lauren classification, (D) tumor size, and (E) H. pylori status. Overall survival in 24 H. pylori-infection negative gastric cancer patients according to (F) microsatellite instability (MSI) and (G) p53 expression.