Department of Pathology, Beijing Chest Hospital, Capital Medical University, 97 Ma Chang, Tongzhou District, Beijing 101149, PR China.
Oncol Rep. 2011 Oct;26(4):877-85. doi: 10.3892/or.2011.1349. Epub 2011 Jun 15.
Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer-related deaths. Aberrance of the two oncogenes MET and SOX2 are frequently encountered in NSCLC. Exons 18 through 21 of the EGFR gene were screened and MET and SOX2 immunostaining was conducted to analyze the immunohistological staining of MET and SOX2 and the EGFR mutation status. One hundred and fifty tissue samples were examined including 57 squamous cell carcinomas (SCCs), 80 adenocarcinomas (ADCs), 9 adenosquamous carcinomas (ADSCs) and 4 large cell carcinomas (LCCs). The 32 NSCLCs harboring an EGFR mutation included 28 ADCs, 3 SCCs and 1 ADSC. A higher level of SOX2 expression appeared in NSCLCs without the EGFR mutation compared to those with EGFR mutation (χ2=9.02, P=0.0027). Of the 28 ADCs, 24 (85.7%) with an EGFR mutation showed low level of SOX2 expression. ADCs with deletion in exon 19 overexpressed MET and showed low levels of SOX2. SOX2 expression was inversely correlated to the expression of MET in NSCLC and mainly present in non-mutated NSCLC (r=-0.42, P<0.0001). There was a tendency for SOX2 to be expressed in SCCs and particularly in the part of SCC among ADSCs, whereas MET was mainly expressed in the part of ADC among ADSCs and ADCs. High level of MET and SOX2 expression were respectively demonstrated in ADCs and SCCs; MET activation was accompanied with exon 19 deletion in ADCs. EGFR and MET coordinate to drive tumorigenesis. Detection of the activation of MET and EGFR may be used for targeted drug therapy.
非小细胞肺癌(NSCLC)是癌症相关死亡的主要原因。MET 和 SOX2 这两个癌基因的异常在 NSCLC 中经常遇到。筛选 EGFR 基因的外显子 18 到 21,并进行 MET 和 SOX2 免疫染色,以分析 MET 和 SOX2 的免疫组织化学染色和 EGFR 突变状态。检查了 150 个组织样本,包括 57 个鳞状细胞癌(SCC)、80 个腺癌(ADC)、9 个腺鳞癌(ADSC)和 4 个大细胞癌(LCC)。32 个携带 EGFR 突变的 NSCLC 包括 28 个 ADC、3 个 SCC 和 1 个 ADSC。与 EGFR 突变的 NSCLC 相比,无 EGFR 突变的 NSCLC 中 SOX2 表达水平更高(χ2=9.02,P=0.0027)。在 28 个 ADC 中,有 24 个(85.7%)EGFR 突变的 ADC 表现出低水平的 SOX2 表达。外显子 19 缺失的 ADC 过表达 MET 并表现出低水平的 SOX2。在 NSCLC 中,SOX2 表达与 MET 的表达呈负相关,主要存在于非突变 NSCLC 中(r=-0.42,P<0.0001)。SOX2 在 SCC 中呈表达趋势,特别是在 ADSC 中的 SCC 部分,而 MET 主要在 ADSC 和 ADC 中的 ADC 部分表达。在 ADC 和 SCC 中分别显示高水平的 MET 和 SOX2 表达;MET 激活伴随着 ADC 中外显子 19 的缺失。EGFR 和 MET 共同协调驱动肿瘤发生。检测 MET 和 EGFR 的激活可用于靶向药物治疗。