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

细胞表面糖蛋白CD44(CD44v)的剪接变异体已被报道与多种人类肿瘤的进展有关。本研究旨在探讨CD44亚型的表达与头颈部鳞状细胞癌临床病理特征的关系。采用免疫组织化学方法检测癌组织中CD44st、v6和v2的表达。癌组织中CD44st、v6和v2的阳性表达分别为100%、85例(95.5%)和59例(66.3%)。V6和V2表达下调与肿瘤细胞分化程度降低有显著相关性(p分别为0.01和0.02)。在淋巴结状态方面，v6表达下调与颈淋巴结转移率显著相关(p=0.02)，v2表达下调与无瘤生存期缩短相关(p=0.01)，而与v6表达下调无相关性(p=0.46)。未发现V2、V6的表达与T分期有明显相关性。COX多因素分析显示，只有v2表达和淋巴结状态是影响预后的独立因素，提示CD44v(v6和v2)表达下调可能是反映HNSCC恶性程度的生物学标志之一。

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.