von Zeidler Sandra Ventorin, de Souza Botelho Talitha, Mendonça Elismauro Francisco, Batista Aline Carvalho
Department of Pathology, Federal University of Espírito Santo, Av, Marechal Campos, 1468 Maruípe, Vitória, ES, Brazil ZIP Code 29,040-090.
BMC Cancer. 2014 Dec 17;14:972. doi: 10.1186/1471-2407-14-972.
Numerous attempts have been made to establish and develop tumor markers that could determine the susceptibility of normal tissues to transform into cancerous ones. To determine whether altered expression patterns of E-cadherin could be an early event in the progression of potentially malignant disorders to oral squamous cell carcinoma, this study aimed to assess the relationship between the immunoexpression of E-cadherin and the different degrees of epithelial dysplasia in oral leukoplakia.
Surgically excised specimens from patients with oral leukoplakia (n=31), oral cavity squamous cell carcinoma with cervical lymph node metastasis (n=12) and normal oral mucosa (n=9) were immunostained for E-cadherin. Oral leukoplakia samples were distributed into low and high risk group according to a binary system for grading oral epithelial dysplasia. Comparative analyses between E-cadherin expression and microscopic features (WHO histological grading and epithelial dysplasia) were performed by Pearson Chi-square test (P<0.05).
Differences in E-cadherin expression were observed between normal oral mucosa and low risk oral leukoplakia (P=0.006), low and high risk oral leukoplakia (P=0.019), and high risk oral leukoplakia and oral cavity squamous cell carcinoma with cervical lymph node metastasis (P=0.0001). In addition, as epithelia undergo dysplastic changes, the risk of malignant transformation increases, and there is a reduction or loss of E-cadherin expression by keratinocytes. Reduced E-cadherin expression was an early phenomenon and it was observed in moderate-severe dysplasia, showing that the loss of epithelial cohesion may be an indicator of progression to oral cavity squamous cell carcinoma.
E-cadherin could be used as a novel biomarker to identify lesions with potential risk for malignant transformation, which may provide opportunities for prophylactic interventions in high risk patient groups.
人们已进行了大量尝试来建立和开发能够确定正常组织转化为癌组织易感性的肿瘤标志物。为了确定E-钙黏蛋白表达模式的改变是否可能是潜在恶性疾病进展为口腔鳞状细胞癌的早期事件，本研究旨在评估E-钙黏蛋白的免疫表达与口腔白斑不同程度上皮发育异常之间的关系。
对31例口腔白斑患者、12例伴有颈部淋巴结转移的口腔鳞状细胞癌患者和9例正常口腔黏膜患者手术切除的标本进行E-钙黏蛋白免疫染色。根据口腔上皮发育异常分级二元系统，将口腔白斑样本分为低风险组和高风险组。通过Pearson卡方检验（P<0.05）对E-钙黏蛋白表达与微观特征（WHO组织学分级和上皮发育异常）进行比较分析。
在正常口腔黏膜与低风险口腔白斑之间（P=0.006）、低风险与高风险口腔白斑之间（P=0.019）以及高风险口腔白斑与伴有颈部淋巴结转移的口腔鳞状细胞癌之间（P=0.0001）观察到E-钙黏蛋白表达存在差异。此外，随着上皮发生发育异常变化，恶性转化风险增加，角质形成细胞中E-钙黏蛋白表达减少或丧失。E-钙黏蛋白表达降低是一种早期现象，在中重度发育异常中即可观察到，表明上皮黏附丧失可能是进展为口腔鳞状细胞癌的一个指标。
E-钙黏蛋白可作为一种新型生物标志物，用于识别具有恶性转化潜在风险的病变，这可能为高危患者群体的预防性干预提供机会。
