p27KIP1 expression in gastric cancer: differential pathways in the histological subtypes associated with Helicobacter pylori infection.

Objective: Decreases in p27(KIP1) and C-MYC expression have been associated with Helicobacter pylori infection. Furthermore, C-MYC seems to be a transcriptional repressor of p27(KIP1). Therefore, in a series of gastric adenocarcinomas we studied the association of p27(KIP1) expression with H. pylori genotype (vacA, cagA, cagE and virB11) and the involvement of C-MYC in this process.

Material And Methods: Expression of p27(KIP1) and C-MYC was determined by immunohistochemistry in 84 gastric adenocarcinoma samples and H. pylori infection and genotype were determined by polymerase chain reaction.

Results: Most p27(KIP1)-negative cases (94.0%) were H. pylori-positive and 44.8% were C-MYC-positive. In the diffuse gastric cancer subtype, p27-negative-C-MYC-positive was the most frequent combination (cluster II), and was associated with the more pathogenic H. pylori strains. Although an association with p27(KIP1) and H. pylori strain was found in the intestinal gastric cancer subtype, negativity for p27(KIP1) and C-MYC markers was the most frequent cluster, followed by cluster II, and both were present, independent of the H. pylori genotype.

Conclusions: Reduced expression of p27(KIP1) was closely linked to H. pylori infection, and was dependent on the more pathogenic strains. Moreover, intestinal and diffuse subtypes showed distinct carcinogenic pathways influenced by H. pylori strains. These data add insight to the differential influence and relevance of H. pylori genotype in gastric cancer development.