CONSISTENT CHROMOSOME-ABNORMALITIES IN SQUAMOUS-CELL CARCINOMA OF THE VULVA

Six squamous cell carcinomas of the vulva (SCV) were karyotyped in short-term culture and in early passages as established cell lines. Each tumor was cytogenetically distinct, contained multiple chromosome rearrangements, and was karyotypically stable in culture. Heterogeneity within individual tumors was manifested by the presence of more than one clonal population, but the clones within each tumor were closely related to one another. Seven consistent chromosome abnormalities found in five of the six tumors were: losses of 3p14-cen, 8pter-p11, 22q13.1-q13.2, and the short arm of the inactive X; chromosome gains involving 3q25-qter and 11q21; and rearrangement breakpoints at 5cen-q12. Ten additional chromosome changes were observed in four of the six SCVs, and together, 22 changes occurred in at least three of the tumors. Two specific losses, 10q23-q25 and 18q22-q23, were present in all four tumors that exhibited biologically aggressive behavior in vivo, but these losses were not found in the tumors of the two long-term survivors. These findings indicate that: 1) SCVs are genetically complex, but homogeneous; 2) loss of 18q22-q23 and loss of 10q23-q25 may be associated with a poor prognosis; and 3) development and progression of SCV appear to result from cumulative effects of altered gene dosage at multiple, consistent loci.