Gains of chromosome region 3q26 in intraepithelial neoplasia and invasive squamous cell carcinoma of the vulva are frequent and independent of HPV status.
OBJECTIVE
Two different forms of vulvar intraepithelial neoplasia (VIN) are recognised: (1) usual-type (bowenoid) VIN, which is related to high-risk papillomavirus infection, and (2) differentiated (simplex) VIN, which is associated with chronic inflammation. The aim of this study was to investigate the presence of chromosome 3q26 gains in the spectrum of precancerous lesions and invasive squamous cell carcinomas (SCCs) of the vulva.


METHODS
3q26 gains were analysed using fluorescence in situ hybridisation in a series of usual-type VINs, VINs of the differentiated type and invasive squamous cell carcinomas. In addition, all cases were examined for human papillomavirus (HPV) DNA, p53 mutations, and p16 and p53 protein expression.


RESULTS
Gains of chromosome 3q26 were present in all VINs of the differentiated type and in 50% of the usual-type VIN lesions. 81% of SCCs 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 imbalance is of additional diagnostic value in difficult cases of HPV-unrelated usual-type VINs and VINs of the differentiated type.
Institute of Pathology, University of Heidelberg, Germany. sebastian.aulmann@med.uni-heidelberg.de
S
S
Aulmann
J
J
Schleibaum
R
R
Penzel
P
P
Schirmacher
G
G
Gebauer
H P
HP
Sinn
D000368:Aged; D002278:Carcinoma in Situ / Q000235:genetics* / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014412:Tumor Virus Infections / Q000150:complications; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000821:virology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53