Frequent hepatocyte growth factor overexpression and low frequency of c-Met gene amplification in human papillomavirus-negative tonsillar squamous cell carcinoma and their prognostic significances
Frequent hepatocyte growth factor overexpression and low frequency of c-Met gene amplification in human papillomavirus-negative tonsillar squamous cell carcinoma and their prognostic significances
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DOI：
10.1016/j.humpath.2014.03.003
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发表时间：
2014-07-01
期刊：
影响因子：
3.3
通讯作者：
Nam, Eun Sook
中科院分区：
文献类型：
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作者：
Kwon, Mi Jung;Kim, Dong Hoon;Nam, Eun Sook
人乳头瘤病毒（HPV）是扁桃体鳞状细胞癌（TSCC）的重要预后因素。HPV阳性和HPV阴性TSCC在预后和化疗/放疗敏感性方面被认为是不同的。然而，到目前为止，还没有研究全面评估这2个疾病亚组的个体预后因素。肝细胞生长因子（HGF）-Met信号通路可以作为预后或治疗反应的预测标志物，尤其是在HPV阴性的TSCC中。因此，我们根据HPV状态研究了TSCC中IMF和c-Met表达的预后价值。对79例经福尔马林固定、石蜡包埋的标本进行HGF和c-Met蛋白表达的免疫组化分析和c-Met基因拷贝数的银原位杂交。在HPV阴性的TSCC中，HGF过表达、区域淋巴结分类和同侧颈淋巴结转移预测总生存率（OS）降低（分别为P = 0.017、P = 0.024和P = 0.003）。后2项也是无进展生存期的独立预后因素（分别为P = 0.023和P = 0.002）。在HPV阳性的TSCC中，大量饮酒和晚期原发肿瘤分类是无进展生存的预测因素，而没有确定OS的独立预后因素。HGF过表达对HPV阴性TSCC的OS有显著影响，但对HPV阳性TSCC无显著影响。HPV阴性/HGF高表达肿瘤的生存结局最差，而HPV阳性/HGF低表达肿瘤的生存结局最好。
Human papillomavirus (HPV) is an important prognostic factor for tonsillar squamous cell carcinoma (TSCC). HPV-positive and HPV-negative TSCCs are considered distinct in terms of prognosis and sensitivity to chemo/radiotherapy. However, to date, no study has thoroughly evaluated the individual prognostic factors for these 2 disease subgroups. Hepatocyte growth factor (HGF)-Met signaling pathway can be a predictive marker for prognosis or therapy response, especially in HPV-negative TSCC. We therefore investigated the prognostic values of IMF and c-Met expression in TSCC according to HPV status. Immunohistochemical analyses of HGF and c-Met protein expression and silver in situ hybridization of c-Met gene copy number were performed in 79 formalin-fixed, paraffin-embedded specimens. In HPV-negative TSCC, HGF overexpression, regional lymph node category, and ipsilateral cervical nodal metastasis predicted decreased overall survival (OS) (P = .017, P = .024, and P = .003, respectively). The latter 2 were also independent prognostic factors for progression-free survival (P = .023 and P = .002, respectively). In HPV-positive TSCC, heavy alcohol consumption and advanced primary tumor category were predictive of progression-free survival, whereas no independent prognostic factor for OS was identified. HGF overexpression had a significant effect on OS in HPV-negative TSCC but not in HPV-positive TSCC. HPV-negative/HGF-high expression tumors exhibited the worst survival outcomes, whereas HPV-positive/HGF-low expression tumors had the most favorable