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From the Departments of Pathology*
and Obstetrics
and Gynecology,
Albany Medical College,
Albany, New York; the Institute for Environmental
Studies,
Louisiana State University, Baton
Rouge, Louisiana; and the Department of Microbiology and
Virology,§
Ruhr-University Bochum,
Bochum, Germany
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 
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.
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  M van Seters, F J W ten Kate, M van Beurden, R H M Verheijen, C J L M Meijer, M P M Burger, and T J M Helmerhorst In the absence of (early) invasive carcinoma, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: new insights in histology and aetiology J. Clin. Pathol., May 1, 2007; 60(5): 504 - 508. [Abstract] [Full Text] [PDF]
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