Baschnagel Andrew M, Tonlaar Nathan, Eskandari Mohammad, Kumar Tripti, Williams Lindsay, Hanna Alaa, Pruetz Barbara L, Wilson George D
Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, USA.
J Oral Pathol Med. 2017 Mar;46(3):208-213. doi: 10.1111/jop.12478. Epub 2016 Jul 21.
PURPOSE/OBJECTIVE(S): To examine the association between CD44 and c-MET expression in relation to p16 and EGFR in patients with head and neck squamous cell carcinoma (HNSCC).
MATERIALS/METHODS: Immunohistochemical staining of CD44, p16, EGFR, and c-MET was performed on 105 locally advanced HNSCC patients treated with chemoradiation. CD44 expression was correlated with c-MET, EGFR, and p16, locoregional control (LRC), distant metastases (DM), disease-free survival (DFS) and overall survival (OS).
High CD44 expression was present in 33% of patients and was associated with non-oropharynx primaries (P < 0.001), high c-MET expression (P < 0.001), p16-negative (P < 0.001) and EGFR-positive tumors (P < 0.001). Fifty-seven percent of CD44 high expressing tumors had high c-MET expression compared to 21% of CD44 low expressing tumors (P < 0.001). High CD44 expression predicted for worse LRC (HR: 2.44; 95% CI: 1.16-5.13; P = 0.018), DFS (HR: 2.61; 95% CI: 1.46-4.67; P = 0.001), and OS (HR: 2.52; 95% CI: 1.30-4.92; P = 0.007) but not DM (P = 0.57) on univariate analysis. Patients with both high CD44 and c-MET expression had a poor prognosis with a 2-year DFS of 30% compared to 70% in the rest of the cohort (P = 0.003). On multivariable analysis, after adjusting for site, T-stage, smoking history, and EGFR status, high c-MET (P = 0.039) and negative p16 status (P = 0.034) predicted for worse DFS, while high CD44 expression did not (P = 0.43).
High CD44 expression is associated with high c-MET expression, p16-negative tumors, and EGFR-positive tumors. The combination of these markers predicts for poor prognosis in HNSCC patients treated with chemoradiation.
研究头颈部鳞状细胞癌（HNSCC）患者中CD44与c-MET表达之间的关联，并与p16和表皮生长因子受体（EGFR）进行相关性分析。
对105例接受放化疗的局部晚期HNSCC患者进行CD44、p16、EGFR和c-MET的免疫组织化学染色。将CD44表达与c-MET、EGFR、p16、局部区域控制（LRC）、远处转移（DM）、无病生存期（DFS）和总生存期（OS）进行相关性分析。
33%的患者CD44高表达，且与非口咽原发肿瘤（P<0.001）、c-MET高表达（P<0.001）、p16阴性（P<0.001）和EGFR阳性肿瘤（P<0.001）相关。57%的CD44高表达肿瘤c-MET高表达，而CD44低表达肿瘤中这一比例为21%（P<0.001）。单因素分析显示，CD44高表达预示LRC较差（风险比[HR]：2.44；95%置信区间[CI]：1.16-5.13；P=0.018）、DFS较差（HR：2.61；95%CI：1.46-4.67；P=0.001）和OS较差（HR：2.52；95%CI：1.30-4.92；P=0.007），但与DM无关（P=0.57）。CD44和c-MET均高表达的患者预后较差，2年DFS为30%，而队列中其他患者为70%（P=0.003）。多因素分析显示，在调整部位、T分期、吸烟史和EGFR状态后，c-MET高表达（P=0.039）和p16阴性状态（P=0.034）预示DFS较差，而CD44高表达则无此关联（P=0.43）。
CD44高表达与c-MET高表达、p16阴性肿瘤和EGFR阳性肿瘤相关。这些标志物的联合预示接受放化疗的HNSCC患者预后不良。
