Cytogenetic characterization of tumors of the vulva and vagina.

Neoplasms of the vulva and vagina account for less than 5% of all female genital tract cancers. Squamous cell carcinoma (SCC) represents more than 70% of the cases in both locales, followed by melanoma, basal cell carcinoma, Paget's disease, and other carcinoma subtypes. Until recently, only few cases had been analyzed by chromosome banding techniques and karyotyped, and also the number subjected to molecular cytogenetic analysis remains low. To understand better the genetic changes harbored by the neoplastic cells in cancer of the vulva and vagina, we analyzed cytogenetically 51 such tumors, finding karyotypic abnormalities in 37. All tumors were analyzed by G-banding, sometimes supplemented by multicolor fluorescence in situ hybridization, and a subset of tumors was also analyzed by comparative genomic hybridization. The two cytogenetically abnormal cases of Paget's disease both had two clones, one with gain of chromosome 7 as the sole change, the other with loss of the X chromosome among, in one case, other aberrations. The four cytogenetically abnormal malignant melanomas (three of the vulva, one of the vagina) presented complex karyotypes with aberrations involving different chromosomes but most often chromosome 1, specifically 1p12-q41. In the 31 cytogenetically abnormal SCCs, different clonal karyotypic abnormalities were seen. Intratumor heterogeneity with multiple clones was observed in 11 cases. The clones were cytogenetically unrelated in eight tumors but related in three, indicating that in the latter clonal evolution had taken place from a single malignantly transformed cell. The main chromosomal imbalances were gains of, or from, chromosome arms 3q, 5p, 8q, 9q, and 19q, and loss from 11q. Breakpoint clusters were seen in 11q13-23, 2q22-35, and 19q13, as well as in the centromeres and pericentromeric bands of chromosomes 3, 8, 9, 13, 14, and 22.