Kyzas Panayiotis A, Stefanou Dimitrios, Batistatou Anna, Agnantis Niki J, Nakanishi Yukihiro, Hirohashi Setsuo, Charalabopoulos Konstantinos
Department of Pathology, University of Ioannina, Medical School, Ioannina, Greece.
Am J Surg Pathol. 2006 Feb;30(2):185-93. doi: 10.1097/01.pas.0000178090.54147.f8.
Dysadherin is a recently characterized cancer-associated cell membrane glycoprotein that has a crucial role to cell-cell adhesiveness. The aim of this study was to examine dysadherin expression in head and neck squamous cell carcinoma (HNSCC). A total of 108 tissue specimens of patients with HNSCC were examined using immunostaining for dysadherin, E-cadherin, and the specific lymphatic endothelium marker D2-40. We quantified dysadherin and E-cadherin expression, assessed intratumoral (ILD) and peritumoral lymphatic density (PLD), and examined the possible associations of all the above parameters with clinicopathologic features and outcome. Finally, we used double staining with dysadherin and D2-40 to examine the expression pattern of dysadherin simultaneously with the lymphovasculature environment of HNSCC. High dysadherin expression was correlated with higher clinical stage (chi2, P = 0.01), with the presence of lymph node metastasis at the time of diagnosis (chi2, P = 0.02), and with increased ILD (chi2, P = 0.001). We observed an impressive reverse association between increased dysadherin expression and decreased E-cadherin expression (chi2, P < 0.001). Surprisingly, dysadherin-positive cancer cells usually gathered around areas of high intratumoral lymphatic vessel concentration, surrounding and invading small intratumoral lymphatics. Higher clinical stage and increased dysadherin expression were found to be the only significant independent prognostic factors for overall survival (hazard ratio, 3.94; 95% confidence interval, 1.09-14.27 for clinical stage; hazard ratio, 3.92; 95% confidence interval, 1.46-10.51 for dysadherin). The loss of intercellular adhesiveness and increased dysadherin expression seems to be related to lymphangiogenesis in HNSCC, but this should be confirmed by additional studies. Dysadherin expression might be a promising prognostic marker for separation of patients at higher risk.
去黏附素是一种最近被鉴定出的与癌症相关的细胞膜糖蛋白，对细胞间黏附起关键作用。本研究旨在检测头颈部鳞状细胞癌（HNSCC）中去黏附素的表达情况。对108例HNSCC患者的组织标本进行免疫染色，检测去黏附素、E-钙黏蛋白以及特异性淋巴管内皮标志物D2-40。我们对去黏附素和E-钙黏蛋白的表达进行定量分析，评估肿瘤内（ILD）和肿瘤周围淋巴管密度（PLD），并研究上述所有参数与临床病理特征及预后的可能关联。最后，我们采用去黏附素和D2-40双重染色，同时检测去黏附素的表达模式以及HNSCC的淋巴管环境。去黏附素高表达与更高的临床分期（χ²，P = 0.01）、诊断时存在淋巴结转移（χ²，P = 0.02）以及ILD增加（χ²，P = 0.001）相关。我们观察到去黏附素表达增加与E-钙黏蛋白表达降低之间存在显著的负相关（χ²，P < 0.001）。令人惊讶的是，去黏附素阳性癌细胞通常聚集在肿瘤内淋巴管高度集中的区域，围绕并侵入小的肿瘤内淋巴管。临床分期较高和去黏附素表达增加是总生存的仅有的显著独立预后因素（风险比，3.94；95%置信区间，临床分期为1.09 - 14.27；风险比，3.92；95%置信区间，去黏附素为1.46 - 10.51）。细胞间黏附丧失和去黏附素表达增加似乎与HNSCC中的淋巴管生成有关，但这一点应通过更多研究加以证实。去黏附素表达可能是用于区分高危患者的一个有前景的预后标志物。
