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Clinicopathological Significance of Fragile Histidine Triad Transcription Protein Expression in Endometrial Carcinomas¹

Departments of Obstetrics and Gynecology [T. Se., T. Sa., M. I.] and Hygiene [K. S.], School of Medicine, Kanazawa University, Kanazawa 920-0934 Japan

Abnormalities in structure and expression of the fragile histidine triad transcription (FHIT) gene have been reported in a variety of cancers, including endometrial cancers. A good correlation between FHIT gene alteration and loss of Fhit expression was observed in endometrial cancers, although those are the selected cases. Therefore, we investigated the association of Fhit expression with clinicopathological features in 111 cases of endometrial cancer. Loss of Fhit expression was associated with high malignant potential, including extensive muscular invasion, advanced surgical stage, high histological grade, nonendometrioid types of adenocarcinoma, negative estrogen receptor status, and p53 overexpression. The presence of personal cancer history was also related to the loss of Fhit with a marginal significance. Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that decreased expression of Fhit was associated with a poor outcome. However, multivariate analysis using the stepwise Cox proportional hazard model showed that whereas lymph node metastasis, advanced stage, and high tumor grade were related to poor survival rates, loss of Fhit expression was not. Consequently, loss of Fhit expression is associated with advanced surgical stage and does not appear to be an independent prognostic factor in endometrial cancers, although a still larger sample of patients will be required to asses this issue definitively.

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