Chromosome 17 Aneusomy Detected by Fluorescence in Situ Hybridization in Vulvar Squamous Cell Carcinomas and Synchronous Vulvar Skin

Abstract

Vulvar squamous cell carcinoma (SCC) affects a spectrum of women with granulomatous vulvar diseases, human papillomavirus (HPV) infections, and chronic inflammatory vulvar dermatoses. To determine whether there is evidence of chromosomal instability occurring in synchronous skin surrounding vulvar SCCs, we investigated abnormalities in chromosome 17 copy number. Samples of SCC, vulvar intraepithelial neoplasia (VIN), and surrounding vulvar skin were obtained from all vulvar excisions performed for squamous neoplasia at Albany Medical College from 1996 to 1997. Histological categorization, fluorescent in situ hybridization (FISH) for the alpha satellite region of chromosome 17, DNA content by image analysis, and Ki-67 labeling were evaluated. Controls of normal vulvar skin not associated with cancer were used for comparison. One hundred ten specimens were obtained from 33 patients with either SCC or VIN 3 and consisted of 49 neoplastic, 52 nonneoplastic, and 9 histologically normal vulvar skin samples. The majority of SCCs (88%) and a minority (18%) of VIN 3 excisions were associated with lichen sclerosus. Normal 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 increased 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 values 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 control vulvar skin (1.5 +/- 0. 05). Concordance of chromosome 17 aneusomy between cancers and synchronous skin lesions was found in 48% of patients. Loss of chromosome 17 was identified 5% of all samples and was significantly associated with women with SCC in situ (HPV-related). Both DNA content and Ki-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 events could be detected in histologically normal skin and inflammatory lesions (lichen sclerosus), chromosomal abnormalities may be a driving force in the early stages of carcinogenesis. Differences in chromosomal patterns (loss or gain) support the concept of at least two pathways in vulvar carcinogenesis.

Chromosomal instability in human mesenchymal stem cells immortalized with human papilloma virus E6, E7, and hTERT genes

“…Structural and numerical aberrations targeting chromosome 17 are often reported in tumors from various tissues (Olaharski et al 2006), whereas the pattern that chromosome 13 is lost and chromosome 17 is stable, was common for the three cell lines in this study, indicating the possibility that the loss of chromosome 13 may play an important role in the chromosomal aberration of hMSCs to acquire growth advantages under the given culturing condition. Similar karyotypic changes were evident in cultured human embryonic stem cells, involving the gain of chromosome 17 or chromosome 12 (Carlson et al 2000;Draper et al 2004). It is thus conjectured that the aneuploidy developed through chromosomal loss from diploid cells arises through different mechanisms from tetraploid intermediate.…”

The most common chromosome aberration detected by high-resolution comparative genomic hybridization in vulvar intraepithelial neoplasia is not seen in vulvar squamous cell carcinoma

“…By using fluorescent in situ hybridization (FISH) Carlson et al (2000) enumerated chromosome 17 in 43 VIN III and VSCC specimens from 33 patients. They found that 76-100 % of the samples were aneuploid with regard to chromosome 17.…”

Comparative analysis of proliferative and genetic alterations in a primary chordoid meningioma and its recurrence using locus-specific probes and AgNOR

“…Hybridization results were examined and analyzed using a Zeiss Axioplan2 fluorescent microscope and Smartcapture 4.1 software. For analysis, we used the criteria found in Carlson et al (39): nuclei of 2-3 different areas were examined in each experiment, totalling 80-120 nuclei. Regions with a high background level or without at least one signal of each probe were not included.…”