Gains of chromosome region 3q26 in intraepithelial neoplasia and invasive squamous cell carcinoma of the vulva are frequent and independent of HPV status
Sebastian Aulmann 1*, Julia Schleibaum 2, Roland Penzel 1, Peter Schirmacher 1, Gerhard Gebauer 2 and Hans Peter Sinn 1
1 Institute of Pathology, University of Heidelberg, Germany
2 Department of Gynecology and Obstetrics, University of Heidelberg, Germany
* To whom correspondence should be addressed. E-mail: sebastian_aulmann{at}med.uni-heidelberg.de.
Accepted 19 May 2008
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Abstract |
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Aims: Two different forms of vulvar intraepithelial neoplasia (VIN) are recognized: usual type (bowenoid) VIN which is related to high-risk papillomavirus infection, and differentiated (simplex) VIN which is associated with chronic inflammation. In this study, we aimed to examine the presence of chromosome 3q26 gains in the spectrum of precancerous lesions and invasive squamous carcinomas of the vulva.
Methods: 3q26 gains were analysed using fluorescence in situ hybridisation (FISH) in a series of usual type VINs, VINs of the differentiated type and invasive squamous cell carcinomas. In addition, all cases were examined for HPV-DNA, p53 mutations as well as p16 and p53 protein expression.
Results: Gains of chromosome 3q26 were present in all VIN of the differentiated type and in 50% of the usual type VIN lesions. 81% of SCC were positive for 3q26 gains irrespective of the HPV status and of the associated precursor lesion. HPV-associated lesions exhibited the typical, strong cytoplasmic p16 accumulation while mutated p53 was only detected in HPV-negative VINs or SCCs and was associated with an overexpression of p53 protein.
Conclusions: Immunohistochemical evaluation of p16 and p53 expression aids in the differential diagnosis of squamous cell alterations of the vulva. However, detection of 3q26 imbalances is of additional diagnostic value in difficult cases of HPV-unrelated usual type VINs and VINs of the differentiated type.
