Loss of Fhit protein expression in high-grade and advanced stage endometrial carcinomas.

BACKGROUND: The fragile histidine triad (FHIT) gene is a candidate tumor suppressor gene located at 3p14.2, and the absence or reduction of Fhit protein expression has recently been reported in various carcinomas. MATERIALS AND METHODS: We examined the expression of Fhit protein in 50 endometrial carcinomas and 19 normal endometrial tissues by immunohistochemistry, and this expression was correlated with clinicopathological parameters, p53 expression, sex steroid receptor status and abnormal FHIT transcripts. RESULTS: All the specimens of normal endometrial gland in the proliferative phase exhibited relatively strong Fhit expression, while most of endometrial tissues in the secretory phase showed weak Fhit expression. In 50 endometrial carcinomas, immunoreactivity for Fhit protein was strong in 21 cases (42%), weak in 22 cases (44%) and partially or totally absent in the remaining 7 cases (14%). There were significant correlations of negative Fhit expression with high tumor grade (p = 0.033) and with advanced stage (p = 0.048). On the other hand, abnormal FHIT transcripts lacking several exons were found in 29% of cases. Neither p53 nor sex steroid receptor status were significantly related with the loss of Fhit expression. CONCLUSION: The loss of Fhit protein expression may be associated with aggressive phenotype of endometrial carcinomas.