Department of Otolaryngology-Head and Neck Surgery - Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada,
Clin Exp Metastasis. 2014 Mar;31(3):307-16. doi: 10.1007/s10585-013-9629-y. Epub 2013 Dec 15.
Overexpression of members of the ErbB receptor family is common in oral squamous cell carcinomas (OSCC); however, their prognostic value for aggressive OSCC has been debated. Extranodal spread to cervical lymph nodes is the most significant prognostic indicator in OSCC. In the present study, we investigated the clinical significance of single versus paired overexpression of members of the ErbB receptor family in 82 OSCC patients with lymph nodes metastasis, with or without capsular rupture (CR) followed by at least 10 years. Immunohistochemistry analysis revealed a common overexpression of ErbB1 (P = 0.021), ErbB2 (P = 0.001), ErbB4 (P = 0.048), as well as MMP-2 (P = 0.043) in OSCC cases with CR+. Increased expression of ErbB1 was associated with MMP-2 in tumors with advanced clinical stages, including poorly differentiated (grade III) tumors (P < 0.050). Vascular embolization was associated with MMP-2 (P = 0.021) and MMP-13 (P = 0.010) overexpression. Survival analysis revealed a lower survival probability in tumors overexpressing ErbB1 (P = 0.038), ErbB4 (P = 0.043), and MMP-12 (P = 0.050). As well a strong association was observed in cases with high risk of recurrence and strong immunostaining for ErbB1 (P = 0.017), ErbB4 (P = 0.008), MMP-1 (P = 0.003), MMP-2 (P = 0.016), MMP-10 (P = 0.041), and MMP-13 (P = 0.005). Stratified multivariate survival analysis revealed a strong prognostic interdependence of ErbB1 and ErbB4 cooverexpression in predicting the worst overall and disease-free survivals (P = 0.0013 and P = 0.0004, respectively). Taken together, these results support a cooperation of ErbB1, ErbB4, and members of the MMP family in predicting OSCC invasion and poor clinical outcomes.
表皮生长因子受体家族成员的过表达在口腔鳞状细胞癌（OSCC）中很常见；然而，它们对侵袭性 OSCC 的预后价值一直存在争议。淋巴结外扩散至颈部淋巴结是 OSCC 最重要的预后指标。在本研究中，我们研究了 82 例有淋巴结转移的 OSCC 患者中，单个或成对过表达表皮生长因子受体家族成员的临床意义，这些患者有或没有包膜破裂（CR），并至少随访 10 年。免疫组化分析显示，CR+的 OSCC 病例中，ErbB1（P = 0.021）、ErbB2（P = 0.001）、ErbB4（P = 0.048）以及 MMP-2（P = 0.043）的过表达常见。在晚期临床分期（包括低分化[III 级]肿瘤）的肿瘤中，ErbB1 的表达增加与 MMP-2 相关（P < 0.050）。血管栓塞与 MMP-2（P = 0.021）和 MMP-13（P = 0.010）的过表达相关。生存分析显示，过表达 ErbB1（P = 0.038）、ErbB4（P = 0.043）和 MMP-12（P = 0.050）的肿瘤的生存概率较低。在高复发风险的病例中，以及在 ErbB1（P = 0.017）、ErbB4（P = 0.008）、MMP-1（P = 0.003）、MMP-2（P = 0.016）、MMP-10（P = 0.041）和 MMP-13（P = 0.005）免疫染色强烈的病例中，观察到强烈的相关性。分层多变量生存分析显示，ErbB1 和 ErbB4 共表达对预测最差的总生存率和无病生存率具有强烈的预后相关性（P = 0.0013 和 P = 0.0004）。总之，这些结果支持 ErbB1、ErbB4 和 MMP 家族成员在预测 OSCC 侵袭和不良临床结局中的合作。
