Prognostic value of CD44 expression in invasive squamous cell carcinoma ofthe vulva

Objective. CD44 is a cell adhesion molecule that binds extracellular matrix . CD44 isoforms arising from alternative mRNA splicing are implicated in tu mor metastases, The aim of our study is to investigate the expression of CD 44 splice variants and its correlation to lymph node metastases and disease -free survival in squamous cell carcinoma (SCC) of the vulva. Methods. Thirty-five cases of SCC of the vulva were evaluated for CD44 spli ce variants -3v, -4v, -5v, and -7v expression by immunocytochemistry. When available one nonmetastatic lymph node (LN) was also studied. In cases with LN metastases, the metastatic LN as well as a nonmetastatic LN from the sa me patient were evaluated, Results. All CD44 variants studied were expressed in all epithelium: normal , dysplastic, and SCC. CD44 variants showed decreased immunostaining in the tumor cells when compared to normal epithelium. Furthermore, intensity of expression of the CD44 isoforms changed within the tissue containing invasi ve cancer. Interestingly, CD44-4v expression was downregulated in the most, differentiated cells within the carcinoma, mainly in patients who had dise ase recurrence or died of disease (P = 0.004). Confirming prior publication s, CD44-5v and -7v expression did not correlate with survival. One hundred percent of metastatic tumors to LNs were immunoreactive with CD44-3v and on ly 1/30 normal LN had CD44-3v expression. Eighty percent of metastatic tumo rs to LNs were immunoreactive for CD44-4v. However, 3 LNs without tumor wer e also immunoreactive with CD44-4v. Conclusion. CD44-4v is a potential molecular marker of disease recurrence i n vulvar carcinoma. A larger multiinstitutional study is needed to evaluate the specificity of CD44-3v expression in LN metastasis. If a larger scale study confirms our findings, a CD44-3v antibody could be used for radioimmu noimaging of occult lymph node metastases in patients with vulvar cancer. ( C) 1999 Academic Press.