Homozygous Deletions Of Exon5, 8 And Protein Expression Of The Tumor-suppressor Gene FHIT In Endometrial Carcinomas

Objective To investigate the homozygous deletions of exon5 and exon5 and protein expression of the tumor-suppressor gene FHIT in endometrial carcinomas and its relations with histopathological features.To explore the potential role of FHIT in the development and progress of endometrial carcinomas. Methods The homozygous deletions of exon5 and exon5 of FHIT gene was detected in 54 cancer samples of EC, 22 corresponding contiguous normal tissues and 46 normal endometrias by PCR. The protein expression of FHIT was detected in the three series by immunohistochemistry.Results The homozygous deletions of FHIT exon5,8 was observed in 14 out of 54 rumors, with a HDs rate of 26%. The rate of exon5 is 20%(9/54), the rate of exon5 is 9%(5/54); Both HDs of exon5 and exon5 was observed in 2 tumors. The HDs rate of FHIT gene in endometrial carcinomas (26%) was significantly higher than that in corresponding contiguous normal tissues (0/22)and normal endometrias(0/46) (P<0.05). Abnormal FHIT expression (reduced or absent) was noted in 35%( 19/54) of tumor cases, no corresponding contiguous normal tissues and normal endometrias showed abnormal FHIT expression. The relationship of HDS and expression was statistically significant(P=0.000 < 0.05).The homozygous deletions of FHIT exon5,8 and abnormal FHIT expression only were observed in EEC, not in NEEC, but there was no statistically significant differences in them(P>0.05). There was no relationship between FHIT gene HDS or expression and histopathological features.Conclusions Loss of FHIT function by HDs or other mechanisms is an event in endometrial tumorigenesis. HDs of FHIT exon5,8 may cause abnormal FHIT expression. HDs of FHIT exon5,8 and abnormal FHIT expression only were observed in EEC, but not related to estrogenic risk factors. FHIT gene alerations may contribute in carcinogenesis in EC, especially in EEC, through an5estrogen-independent pathway.