Simultaneous squamous cell carcinomas of the uterine cervix and upper genital tract: loss of heterozygosity analysis demonstrates clonal neoplasms of cervical origin

Abstract

Five cases of cervical squamous cell carcinoma with synchronous superficial squamous cell carcinoma in the upper genital tract were genetically analyzed to demonstrate the possibility of a clonal neoplastic process. In these cases, the cervical lesions were squamous cell carcinoma in situ (cases 1, 2, and 3) and invasive squamous cell carcinoma (cases 4 and 5). Loss of heterozygosity (LOH) analyses with a panel of microsatellite markers revealed a monoclonal process in four of the five cases. Homogeneous LOH throughout the microdissected lesions was most frequently detected on 6p and 6q (3 cases), followed by 11p and 11q (2 cases), loci known to be commonly lost in typical cervical squamous cell carcinoma. In two cases, genetic progression in terms of additional LOH was found in the upper genital tract but not in the cervix. Most of these squamous cell carcinomas were monoclonal neoplasms originating from the cervical mucosa with subsequent superficial migration of the tumor clone to the upper genital mucosa, and in some cases, genetic progression.