Oncosuppressor proteins of fragile sites are reduced in cervical cancer.

FHIT and WWOX are tumor suppressor genes that span the common fragile sites FRA3B and FRA16D, respectively. To analyze possible synergisms among these genes in cervical cancer progression, we considered 159 cervical intraepithelial neoplasias, and 58 invasive squamous cell carcinomas of the uterine cervix. All cases were previously selected as high risk HPV. FHIT and WWOX proteins were examined by immunohistochemistry and their expression was inversely correlated with precancerous vs. invasive lesions. Statistics among biological markers indicated an association between FHIT and WWOX. Protein expression of these two genes was also absent or reduced in cancer cell lines. Thus, WWOX may be considered as a novel important genetic marker in cervical cancer and the association between the altered expression of FHIT and WWOX may be a critical event in the progression of this neoplasia.