Immunohistochemical detection of CD44v expression in preneoplastic and neoplastic lesions of the vulva.

Purpose: The cell surface glycoproteins of the CD44 family are divided into standard CD44 (CD44 s) and splice variants of CD44 (CD44v). In normal human tissues CD44v expression is mainly restricted to certain epithelia. Its expression could also be demonstrated in human gynaecological malignancies by immunohistochemistry and semi-quantitative reverse transcription PCR. In this study we investigated the expression of CD44v epitopes encoded by the variant exons v5, v6 and v3 to v10 in preneoplastic and neoplastic lesions of the vulva. Method and material: We investigated the expression of CD44v in biopsies of 30 patients with VIN and 11 patients with vulval carcinoma by immunohistochemical APAAP staining. In addition HPV-DNA was tested using PCR on 10 mu m thick paraffin sections. We examined samples for HPV 6 and 11 as well as for 16 and 18. Results: In normal vulval keratinocytes CD44v5, CD44v6 and CD44v3-v10 is present in the membranes of the lower two thirds of the epithelium. The same distribution pattern of CD44v is seen in mild and moderate intraepithelial neoplasia of the vulva (VIN I/II). In severe intraepithelial neoplasia of the vulva (VIN III) we observed alterations in the CD44v expression in comparison to normal vulval tissue. The detection of CD44v isoforms is reduced. In squamous cell carcinoma of the vulva CD44v5, CD44v6 and CD44v3-v10 is present in the membranes of carcinoma cells in non-keratinizing areas. In poor differentiated areas of squamous cell carcinoma we found a loss of CD44v expression. CD34v expression is independent of age, histological subtype of VIN III or vulval carcinoma and detection of HPV-DNA type 6/11, 16 and 18. Conclusion: According to our first immunohistochemical results, CD44v expression is not correlated to poor clinical outcome of patients with preneoplastic and neoplastic diseases of the vulva.