Cui Xiaobin, Li Su, Li Tingting, Pang Xuelian, Zhang Shumao, Jin Jing, Hu Jianming, Liu Chunxia, Yang Lan, Peng Hao, Jiang Jinfang, Liang Weihua, Suo Jing, Li Feng, Chen Yunzhao
Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine Shihezi, China ; Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine Shihezi, China.
Int J Clin Exp Pathol. 2014 Apr 15;7(5):2382-91. eCollection 2014.
Extracellular signal-regulated kinases (ERKs) are activated by the MAPK pathway. ERKs are downstream effectors of the epidermal growth factor receptor (EGFR), which belongs to the receptor tyrosine kinases family. Studies on the activation of the EGFR-ERK pathway in Kazakh patients with esophageal squamous cell carcinoma (ESCC) have not been reported. Using immunohistochemical staining on tissue microarrays, we investigated the protein expression of EGFR and ERK in 90 ethnic Kazakh patients with ESCC and 48 adjacent normal esophageal tissues (NETs). EGFR and ERK1 expression was localized in the cytoplasm, whereas ERK2 expression was localized in the nucleus. Both were more highly expression in the ESCC tissues than in the NETs, and the difference was considered significant (P=0.003, 0.002, and 0.005, respectively). ERK1 and EGFR expression was positively correlated with lymph nodes metastasis (P=0.011 and 0.013, respectively). ERK1 staining was also significantly associated with tumor-node-metastases stage of ESCC (P=0.044). ERK2 staining was significantly associated with Histological grade (P=0.012). Furthermore, ERK1 and EGFR expression in the ESCC tissues were positively correlated (r=0.413, P<0.001); EGFR was more highly expressed in the ESCC tissues with high ERK1 expression than in the ESCC tissues with low ERK1 expression (4.95±0.57 vs. 3.21±0.35, P=0.01). This study is thus far the first to demonstrate the correlation between EGFR overexpression and ERK overexpression in Kazakh patients with ESCC. This correlation suggests that the EGFR-ERK signaling pathway participates in ESCC progression and can thus be used as a prognostic marker.
细胞外信号调节激酶（ERKs）由丝裂原活化蛋白激酶（MAPK）途径激活。ERKs是表皮生长因子受体（EGFR）的下游效应器，EGFR属于受体酪氨酸激酶家族。目前尚未见关于哈萨克族食管鳞状细胞癌（ESCC）患者EGFR-ERK途径激活的研究报道。我们采用组织芯片免疫组化染色法，对90例哈萨克族ESCC患者及48例癌旁正常食管组织（NETs）中EGFR和ERK的蛋白表达进行了研究。EGFR和ERK1表达定位于细胞质，而ERK2表达定位于细胞核。二者在ESCC组织中的表达均高于NETs，差异有统计学意义（P值分别为0.003、0.002和0.005）。ERK1和EGFR表达与淋巴结转移呈正相关（P值分别为0.011和0.013）。ERK1染色也与ESCC的肿瘤-淋巴结-转移分期显著相关（P = 0.044）。ERK2染色与组织学分级显著相关（P = 0.012）。此外，ESCC组织中ERK1和EGFR表达呈正相关（r = 0.413，P < 0.001）；ERK1高表达的ESCC组织中EGFR表达高于ERK1低表达的ESCC组织（4.95±0.57 vs. 3.21±0.35，P = 0.01）。本研究是首次证明哈萨克族ESCC患者中EGFR过表达与ERK过表达之间存在相关性。这种相关性表明EGFR-ERK信号通路参与了ESCC的进展，因此可作为一种预后标志物。
