Differences in proximal (cardia) versus distal (antral) gastric carcinogenesis via the retinoblastoma pathway.
OBJECTIVE
Disruption of cell cycle regulation is a critical event in carcinogenesis, and alteration of the retinoblastoma (pRb) tumour suppressor pathway is frequent. The aim of this study was to compare alterations in this pathway in proximal and distal gastric carcinogenesis in an effort to explain the observed striking epidemiological differences.


METHODS
Immunohistochemistry was performed to investigate expression of p16 and pRb in the following groups of both proximal (cardia) and distal (antral) tissue samples: (a) biopsies showing normal mucosa, (b) biopsies showing intestinal metaplasia and, (c) gastric cancer resection specimens including uninvolved mucosa and tumour.


RESULTS
In the antrum there were highly significant trends for increased p16 expression with concomitant (and in the group of carcinomas inversely proportional) decreased pRb expression from normal mucosa to intestinal metaplasia to uninvolved mucosa (from cancer resections) to carcinoma. In the cardia, there were no differences in p16 expression between the various types of tissue samples whereas pRb expression was higher in normal mucosa compared with intestinal metaplasia and tissue from cancer resections.


CONCLUSIONS
Alterations in the pRb pathway appear to play a more significant role in distal gastric carcinogenesis. It may be an early event in the former location since the trend towards p16 overexpression with concomitant pRb underexpression was seen as early as between normal mucosa and intestinal metaplasia. Importantly, the marked differences in expression of pRb and p16 between the cardia and antrum strongly support the hypothesis that tumours of the two locations are genetically different which may account for some of the observed epidemiological differences.
Gulmann
Christian
C
Department of Pathology, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. cgulmann@rcsi.ie
Hegarty
Helen
H
Grace
Antoinette
A
Leader
Mary
M
Patchett
Stephen
S
Kay
Elaine
E
D000328:Adult; D000368:Aged; D001706:Biopsy; D002299:Cardia / Q000378:metabolism / Q000473:pathology*; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011706:Pyloric Antrum / Q000378:metabolism / Q000473:pathology*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein