Nishizawa Aya, Nakanishi Yukihiro, Yoshimura Kimio, Sasajima Yuko, Yamazaki Naoya, Yamamoto Akifumi, Hanada Katsumi, Kanai Yae, Hirohashi Setsuo
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Cancer. 2005 Apr 15;103(8):1693-700. doi: 10.1002/cncr.20984.
The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, the authors reported a novel cell membrane glycoprotein, dysadherin, which has an anti-cell-cell adhesion function and down-regulates E-cadherin.
Expression of both dysadherin and E-cadherin was investigated immunohistochemically in 115 patients with cutaneous malignant melanoma to determine the correlation between the 2 molecules and their associations with both patient survival and the clinicopathologic features of the tumors.
Dysadherin and E-cadherin were expressed at the cell membranes of melanoma cells. Fifty-two percent of the tumors showed dysadherin immunopositivity, and 91% of the tumors showed reduced E-cadherin immunopositivity. There was no significant inverse correlation between dysadherin expression and E-cadherin expression. Increased dysadherin expression was significantly correlated with nodular subtype (P = 0.042), Clark level (P < 0.001), tumor thickness (P < 0.001), ulceration (P = 0.008), lymph node metastasis (P < 0.001), high TNM classification (P < 0.001), and poor patient survival (P < 0.001). Multivariate analysis of patient survival revealed that increased dysadherin expression was a significant predictor of poor survival (P < 0.001).
Thus, increased expression of dysadherin was a significant indicator of poor prognosis in patients with cutaneous malignant melanoma.
E-钙黏蛋白介导的细胞黏附系统常通过多种机制失活,并参与多种癌症的肿瘤进展。最近,作者报道了一种新型细胞膜糖蛋白——功能障碍黏附素,它具有抗细胞间黏附功能并下调E-钙黏蛋白。
对115例皮肤恶性黑色素瘤患者进行免疫组织化学研究,检测功能障碍黏附素和E-钙黏蛋白的表达,以确定这两种分子之间的相关性及其与患者生存率和肿瘤临床病理特征的关系。
功能障碍黏附素和E-钙黏蛋白在黑色素瘤细胞的细胞膜上表达。52%的肿瘤显示功能障碍黏附素免疫阳性,91%的肿瘤显示E-钙黏蛋白免疫阳性降低。功能障碍黏附素表达与E-钙黏蛋白表达之间无显著负相关。功能障碍黏附素表达增加与结节亚型(P = 0.042)、克拉克分级(P < 0.001)、肿瘤厚度(P < 0.001)、溃疡(P = 0.008)、淋巴结转移(P < 0.001)、高TNM分期(P < 0.001)及患者生存率低(P < 0.001)显著相关。对患者生存率的多因素分析显示,功能障碍黏附素表达增加是生存率低的显著预测因素(P < 0.001)。
因此,功能障碍黏附素表达增加是皮肤恶性黑色素瘤患者预后不良的重要指标。