Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Ann Oncol. 2011 Aug;22(8):1886-93. doi: 10.1093/annonc/mdq756. Epub 2011 Feb 22.
Mounting evidence suggests that recurrence of resected head and neck squamous cell carcinomas (HNSCCs) is due to the outgrowth of unrecognized residual tumor cells as well as to the premalignant and/or precursor-field epithelial cells. We studied the impact of processes triggered by HNSCC surgery in stimulating both residual tumor cells [demonstrated to overexpress epidermal growth factor receptor (EGFR)], and premalignant cells surrounding the resected lesion.
EGFR expression/activation by immunohistochemistry/biochemistry and gene status by FISH were investigated in 23 primary HNSCCs and surrounding tissues. The ability to induce cell proliferation of wound healing drainages collected from 12 relapsed and 11 not relapsed patients was evaluated by a colorimetric assay in squamous cell carcinoma cell lines A431 (carrying EGFR amplification) and CAL27 (carrying three EGFR copies) in the presence/absence of EGFR therapeutic inhibitors.
Primary tumors showed intermediate/high EGFR expression (91%), EGFR phosphorylation and EGFR-positive FISH (35%). Normal, metaplastic and dysplastic epithelium surrounding the resected tumor displayed EGFR overexpression. EGFR activation and gene amplification were observed in normal and dysplastic epithelium, respectively. Each tested wound healing drainage induced the cells to proliferate and the proliferation was significantly higher in relapsed compared with not relapsed HNSCC patients (P = 0.02 and P = 0.03). Anti-EGFR treatments inhibited the drainage-induced proliferation, with the highest inhibitory efficiency by cetuximab on A431 cells, while CAL27 cell growth was more efficiently inhibited by tyrosine kinase inhibitors.
Surgery could favor the proliferation of cells showing EGFR overexpression/activation/amplification such as residual tumor cells and/or precursor-field epithelial cells already present after surgery. Treatment with anti-EGFR reagents inhibits wound-induced stimulation, according to the EGFR family status.
越来越多的证据表明，切除的头颈部鳞状细胞癌（HNSCC）的复发是由于未被识别的残留肿瘤细胞以及癌前和/或前体细胞的生长。我们研究了 HNSCC 手术引发的过程对刺激残留肿瘤细胞（已证明其过度表达表皮生长因子受体（EGFR））和切除病变周围的癌前细胞的影响。
通过免疫组织化学/生物化学检测 23 例原发性 HNSCC 及其周围组织中的 EGFR 表达/激活，通过 FISH 检测基因状态。通过比色法评估从 12 例复发和 11 例未复发患者收集的伤口愈合引流物在存在/不存在 EGFR 治疗抑制剂的情况下对携带 EGFR 扩增的鳞状细胞癌细胞系 A431（携带 EGFR 扩增）和 CAL27（携带三个 EGFR 拷贝）的细胞增殖的诱导能力。
原发性肿瘤显示中等/高 EGFR 表达（91%），EGFR 磷酸化和 EGFR 阳性 FISH（35%）。切除肿瘤周围的正常、化生和发育不良上皮均显示 EGFR 过表达。EGFR 激活和基因扩增分别在正常和发育不良上皮中观察到。每个测试的伤口愈合引流均诱导细胞增殖，且在复发的 HNSCC 患者中增殖明显高于未复发的患者（P=0.02 和 P=0.03）。抗 EGFR 治疗抑制引流诱导的增殖，其中西妥昔单抗对 A431 细胞的抑制效率最高，而酪氨酸激酶抑制剂对 CAL27 细胞生长的抑制效率更高。
手术可能有利于增殖已存在于手术后的残留肿瘤细胞和/或前体细胞中的细胞，这些细胞表现出 EGFR 过表达/激活/扩增。根据 EGFR 家族状态，用抗 EGFR 试剂治疗可抑制伤口诱导的刺激。
