Chromosome 17 aneusomy detected by fluorescence in situ hybridization in vulvar squamous cell carcinomas and synchronous vulvar skin

Vulvar squamous cell carcinoma (SCC) affects a spectrum of women with granu lomatous vulvar diseases, human papillomavirus (HPV) infections, and chroni c inflammatory vulvar dermatoses. To determine whether there is evidence of chromosomal instability occurring in synchronous skin surrounding vulvar S CCs, me investigated abnormalities in chromosome 17 copy number. Samples of SCC, vulvar intraepithelial neoplasia (VIN), and surrounding vulvar skin w ere obtained from all vulvar excisions performed for squamous neoplasia at Albany Medical College from 1996 to 1997, Histological categorization, fluo rescent ill situ hybridization (FISH) for the cu satellite region of chromo some 17, DNA content by image analysis, and Ki-67 labeling were evaluated. Controls of normal vulvar skin not associated with cancer were used for com parison, One hundred ten specimens were obtained from 33 patients with eith er SCC or VIN 3 and consisted of 49 neoplastic, 52 nonneoplastic, and 9 his tologically normal vulvar skin samples. The majority of SCCs (88%) and a mi nority (18%) of VIN 3 excisions were associated with lichen sclerosus, Norm al vulvar skin controls did not exhibit chromosome 17 polysomy (cells with more than four FISH signals), whereas 56% of normal vulvar skin associated with cancer did. Moreover, the frequency of polysomy significantly increase d as the histological classification progressed from normal to inflammatory to neoplastic lesions. The largest mean value and variance for chromosome 17 copy number was identified in SCCs (2.4 +/- 1.0) with intermediate value s identified, in decreasing order, for SCC in situ (2.1 +/- 1.0), VIN 2 (2. 1 +/- 0.8), lichen sclerosus (2.0 +/- 0.5), lichen simplex chronicus (1.9 /- 0.4), and normal skin associated with SCC (1.8 +/- 0.4) compared with co ntrol vulvar skin (1.5 +/- 0.05). Concordance of chromosome 17 aneusomy bet ween cancers and synchronous skin lesions was found in 48% of patients. Los s of chromosome 17 was identified 5% of all samples and was significantly a ssociated with women with SCC in situ (HPV-related). Both DNA content and K i-67 labeling positively and significantly correlated with mean chromosome 17 copy number (r = 0.1, P = 0.007). A high degree of genetic instability ( aneuploidy) occurs in the skin surrounding vulvar carcinomas. As these even ts could be detected in histologically normal skin and inflammatory lesions (lichen sclerosus), chromosomal abnormalities may be a driving force in th e early stages of carcinogenesis. Differences in chromosomal patterns (loss or gain) support the concept of at least two pathways in vulvar carcinogen esis.