Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
Department of Pathology, William Beaumont Hospital, Royal Oak, Michigan.
Int J Radiat Oncol Biol Phys. 2014 Mar 1;88(3):701-7. doi: 10.1016/j.ijrobp.2013.11.013.
To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation.
Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS).
Fifty-one percent of patients were positive for p16, and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients.
c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16-negative patients but not in p16-positive patients. c-Met predicted for worse outcome regardless of EGFR status.
研究 c-Met 表达与局部晚期头颈部鳞状细胞癌（HNSCC）患者 p16 和表皮生长因子受体（EGFR）在接受根治性同期放化疗中的关系及其预后意义。
检索了 107 例接受放化疗的 HNSCC 患者的存档组织，构建了组织微阵列。对 c-Met、p16 和 EGFR 进行免疫组织化学染色。分析 c-Met 表达与 p16、EGFR、临床特征及局部区域控制（LRC）、远处转移（DM）、无病生存（DFS）和总生存（OS）等临床终点的相关性。
51%的患者 p16 阳性，53%的患者 EGFR 阳性。p16 阴性（P≤.001）和 EGFR 阳性（P=.019）均预示着较差的 DFS。93%的患者 c-Met 染色阳性。患者分为低（0、1 或 2+强度）或高（3+强度）c-Met 表达。单因素分析显示，高 c-Met 表达预示着较差的 LRC（风险比 [HR] 2.27；95%CI，1.08-4.77；P=.031）、DM（HR 4.41；95%CI，1.56-12.45；P=.005）、DFS（HR 3.00；95%CI，1.68-5.38；P<.001）和 OS（HR 4.35；95%CI，2.13-8.88；P<.001）。多因素分析显示，在调整部位、T 分期、吸烟史和 EGFR 状态后，只有高 c-Met 表达（P=.011）和 p16 阴性（P=.003）与较差的 DFS 相关。高 c-Met 表达在 EGFR 阳性（P=.032）和阴性（P=.008）患者中均与较差的 DFS 相关。在 p16 阴性患者中，高 c-Met 表达患者的 DFS 较差（P=.036），而低 c-Met 表达患者的 DFS 较好。c-Met 表达与 p16 阳性患者的任何结局均无相关性。
c-Met 在大多数局部晚期 HNSCC 病例中表达，高 c-Met 表达预示着较差的临床结局。高 c-Met 表达与 p16 阴性患者的较差 DFS 相关，但与 p16 阳性患者无关。c-Met 表达与 EGFR 状态无关，与较差的预后相关。
