Reduced Fhit expression occurs in the early stage of esophageal tumorigenesis: No correlation with p53 expression and apoptosis

The FHITgene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene involved in multiple tumors, including es ophageal carcinoma. We analyzed Fhit expression using an immunohistochemica l method in invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in p araffin sections of 75 esophageal squamous cell carcinomas (ESCs) to furthe r elucidate the role of Fhit protein in esophageal carcinogenesis. In addit ion, we also examined whether Fhit expression correlated with p53 expressio n and apoptosis. Compared to adjacent normal mucosa, significant loss or re duction of Fhit expression was noted in 67 of 75 (89.3%) invasive ESCs, in 13 of 19 (68.4%) CIS lesions, and in 10 of 23 (43.5%) dysplastic lesions. T here was a progressive loss or reduction of Fhit expression with progressiv e increases in the severity of histopathological changes (p<0.001). However , there was no association between Fhit expression and clinicopathological findings, including tumor stage, lymph node metastasis, or overall survival . Moreover, Fhit expression was not significantly associated with p53 expre ssion and apoptosis. These results indicate that abnormal Fhit expression i s a common event in the early stage of ESC development and may occur indepe ndently of p53 expression and apoptosis mechanisms. Copyright (C) 2001 S.Ka rger AG, Basel.