Immunohistochemical expression of Fhit protein in Helicobacter pylori related chronic gastritis, gastric precancerous lesions and gastric carcinoma:: correlation with conventional clinicopathologic parameters

Objective Our purpose was to investigate the immunohistochemical expression of Fhit protein in chronic Helicobacter pylori related gastritides, gastric epithelial dysplasia and gastric carcinoma. Design Because a subset of chronic K pylori related gastritides, precancerous lesions and gastric tumours were found to be either entirely negative or to minimally express Fhit protein, it is suggested that alteration of the carcinogen susceptible fragile region within the FHIT gene is an early event in a subset of gastric adenocarcinomas. Methods We carried out immunohistochemical tests on archived material of formalin fixed, paraffin embedded tissues, using the anti-FHIT antibody and the streptavidin-biotin-peroxidase method, in a total of 135 gastric lesions (76 biopsies and 59 surgically resected gastric adenocarcinomas). Results In this study, 79% of H. pylori related gastritides showed that the Fhit protein was either completely absent or there was a marked reduction of immunostaining. Similar results were obtained for 76.4% of cases of chronic gastritides with low and high-grade dysplasia, and 56% of gastric adenocarcinomas. A negative result for Fhit protein immunostaining was strongly associated with H. pylori infection (P = 0.0001) and with epithelial dysplasia (P = 0.01) but not with intestinal metaplasia or degree of activity. Additionally, negative or reduced immunostaining for Fhit was associated with the degree of dysplasia and progress of a subset of these lesions to infiltrating adenocarcinoma (P= 0.02). In gastric adenocarcinomas negative or weak immunostaining of the Fhit protein correlated with the histological grade (P = 0.01) and clinical stage of the disease (P = 0.01). Conclusions Our results suggest that, because Fhit protein immunostaining is completely absent in (1) the majority of H. pylori related chronic gastritides, (2) a subset of gastric dysplastic lesions, and (3) a proportion of primary gastric adenocarcinomas, irrespective of histological type, it can play an important role in the early development and progression of some gastric cancers. Eur J Gastroenterol Hepatol 15:515-523 (C) 2003 Lippincott Williams Wilkins.