The relation of pepsinogen group II (PGII) expression to intestinal metaplasia and gastric cancer

AIMS: A substantial minority of intestinal metaplasia (IM)-associated stomach cancers express a gastric product-pepsinogen group II (PGII). The aim of this study was to examine PGII expression as it relates to IM and to tumour heterogeneity. METHODS AND RESULTS: The extent of IM was divided into four levels: none, minimal, moderate, extensive. Stomach specimens (N = 165) were stained for PGII and two tumour markers, epidermal growth factor receptor (EGFr) and p53. PGII was more likely to be expressed with moderate or extensive IM than with minimal or no IM (P = 0.05). Cancers that expressed PGII were more likely to be of high stage than those that did not (P = 0.035). Of 25 cases that expressed all three markers (PGII, EGFr, p53), 20 (80%) had stage 3 or 4 disease, compared with 11 (37%) advanced cancers expressing none of the markers (P = 0.001). Cancers expressing one or two markers were between these extremes. CONCLUSIONS: PGII+ cancers in IM-associated gastric cancers may derive from residual gastric glands, or may arise from postinduction reversion to a gastric phenotype from intestinalized cells. This is supported by the more frequent association of PGII expression with the most extensive degrees of IM and its association with high-stage cancers that display heterogeneity in tumour marker expression.