Fhit protein expression in endometrial cancers: no correlation with histological grade

The genes specifically involved in endometrial cancers have not yet been discovered. The FHIT gene, a tumour suppressor located at 3p14.2, is altered in many human tumours, including those derived from the female genital tract. We have thus investigated the status of Fhit protein expression in endometrial carcinomas (EC), and its association with histological grade of malignancy in order to determine if Fhit expression is inactivated in EC and if so, whether it is inactivated during initiation or progression. Recent studies have reported that alteration in the FHIT locus detected by DNA and RNA analysis is well correlated with loss of Fhit protein expression in tumours. Thus, we characterised Fhit protein expression as an indication of FHIT gene status in 35 cases of EC of different histological grade (G1: 13 cases; G2: 14 cases; G3: 8 cases). In our group of cancers, Fhit protein expression was absent or reduced in 37% (13/35) of EC. The first 13 cases, judged as G1, showed Fhit deficiency in approximately 38.5% of cases (5/13). For G2 and G3 tumours these numbers were similar and accounted for approximately 35.7% (5/14) and approximately 37.5% (3/8), respectively. No statistical difference was found for Fhit expression among the various groups of tumours, which allowed us to conclude that morphological grade does not seem to be an important factor. Our results suggest that Fhit inactivation is an early event in carcinogenesis of the endometrium. As this observation is contrary to some already published reports, another independent study with larger amounts of material is necessary to determine this issue definitely.