PROGNOSTIC SIGNIFICANCE OF EXPRESSION OF CD44 VARIANTS IN HEAD AND NECK CANCER

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Splice variants of the cell surface glycoprotein CD44(CD44v)have been reported to be involved in the progression of various human tumors. The aim of this study is to determine the correlation between the expression of CD44 isoforms and the clinicopathological features of head and neck squamous cell carcinomas(HNSCCs). The expression of CD44v was evaluated immunohistochemically in paraffin-embedded tissues from 89 primary lesions, using monoclonal antibodies against CD44 standard(CD44st), variant 6(v6)and variant 2(v2).Cancer tissues from 89(100%), 85(95.5%)and 59(66.3%)patients showed positive immunoreactivity for CD44st, v6 and v2, respectively. Significant correlations were observed between the down-regulation of v6 or v2 and poorer differentiation of the tumor cells(p=0.01 and 0.02, respectively). As for lymph node status, down-regulation of v6 but not v2 was correlated significantly with increased rate of metastasis to the cervical lymph nodes(p=0.02).Down-regulation of v2 expression was correlated with shorter disease free survival(p=0.01), but no such correlation with v6 was seen in these tumors(p=0.46). We could not find any significant correlation between expression of v2 or v6 and T stage. Cox's multivariate analysis revealed that only v2 expression and lymph node status were independent prognostic factors.These findings suggest that down-regulation of expression of CD44v(v6 and v2)may be one of the biological markers for the degree of malignancy in HNSCCs.