Prognostic value of CD44 splice variants in human stage III cervical cancer

The expression of specific cell adhesion molecule CD44 isoforms (splice variants) has been shown to be associated with poor prognosis in human malignancies, such as breast cancer. We used three different variant exon sequence-specific murine monoclonal antibodies to epitopes encoded by exons v5, v6 or v7-v8 of human variant CD44, to study the expression of CD44 splice variants by immunohistochemistry in human stage III cervical cancer. We investigated 40 pretreatment punch biopsies of cervical cancer FIGO stage III. CD44 splice variants CD44v5, CD44v6 and CD44v7-8 were detected by means of immunohistochemistry in 90%, 55% and 25%, respectively. CD44 epitopes encoded by exon v5 were not correlated with prognosis. Expression of CD44 splice variants containing epitopes encoded by exon v6 were correlated with significantly poorer prognosis (Mantel test, P = 0.008). Five-year survival rates with or without CD44v6 expression were 20% versus 71%, respectively. Expression of CD44v7-8 was also correlated with significantly poorer overall survival (Mantel test, P = 0.02). Expression of CD44 splice variants containing epitopes encoded by exons v7-v8 and especially exon v6 is associated with significantly poorer prognosis in stage III cervical cancer patients.