Prognostic Significance of Epidermal Growth Factor Receptor Phosphorylation and Mutation in Head and Neck Squamous Cell Carcinoma
Prognostic Significance of Epidermal Growth Factor Receptor Phosphorylation and Mutation in Head and Neck Squamous Cell Carcinoma
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DOI：
10.1634/theoncologist.2009-0058
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发表时间：
2009-01-01
期刊：
影响因子：
5.8
通讯作者：
Urashima, Mitsuyoshi
中科院分区：
文献类型：
--
作者：
Hama, Takanori;Yuza, Yuki;Urashima, Mitsuyoshi
表皮生长因子受体（EGFR）的分子状态在头颈部鳞状细胞癌（HNSCC）中的研究不如在肺癌中的研究。我们检测了HNSCC患者EGFR突变的频率以及EGFR蛋白的表达/磷酸化状态。此外，我们试图阐明EGFR分子状态与患者特征和无病生存率之间的关系。在这项前瞻性队列研究中，从82例未接受EGFR分子靶向治疗的连续患者中获得临床数据和样本。对全长EGFR进行测序，并通过Western印迹法测量EGFR蛋白的表达和磷酸化。在6例HNSCC中发现了4个新的突变（E709 K、V765 G、Ins 770 G和G1022 S）和1个肺癌中已知的突变（L 858 R）（7%），但我们在本研究中未发现EGFR胞外结构域的任何突变，如EGFRvIII。基于Ba/F3细胞的使用，E709 K和Ins 770 G以及L 858 R似乎是功能性突变。就患者特征而言，转移淋巴结的数量和淋巴结分期与EGFR磷酸化相关。在研究期间，没有EGFR突变患者复发。排除突变病例，肿瘤样本显示EGFR磷酸化的患者比没有EGFR磷酸化的患者复发明显更早。在使用考克斯比例风险模型校正EGFR蛋白的突变和过表达后，该发现仍然显著。总之，无突变的磷酸化EGFR可能是HNSCC患者预后不良的标志物。肿瘤学家2009; 14：900-908
The molecular status of the epidermal growth factor receptor ( EGFR) has not been as well studied in head and neck squamous cell carcinoma (HNSCC) as in lung cancer. We examined the frequencies of EGFR mutations as well as the expression/phosphorylation status of the EGFR protein in HNSCC patients. Moreover, we tried to elucidate associations between EGFR molecular status and patient characteristics and disease-free survival. In this prospective cohort study, clinical data and samples were obtained from 82 consecutive patients who had not been treated with EGFR molecular targeting therapy. Full-length EGFR was sequenced, and expression and phosphorylation of the EGFR protein were measured by Western blotting. Four novel mutations (E709K, V765G, Ins770G, and G1022S) and one mutation well-known in lung cancer (L858R) were identified in six HNSCC samples (7%), but we could not find any mutations in the extracellular domain of EGFR, such as EGFRvIII, in this study. E709K and Ins770G as well as L858R appear to be functional mutations based on the use of Ba/F3 cells. In terms of patient characteristics, the number of metastatic lymph nodes and node stage were associated with phosphorylation of EGFR. No patients with EGFR mutations relapsed during the study period. Excluding mutated cases, patients whose tumor samples showed phosphorylated EGFR relapsed significantly earlier than those without phosphorylated EGFR. This finding was still significant after adjusting for mutation and overexpression of EGFR protein using the Cox proportional hazard model. In conclusion, phosphorylated EGFR without mutations may be a marker of poor prognosis in patients with HNSCC. The Oncologist 2009; 14: 900-908