阴茎癌中表皮生长因子受体、切除修复交叉互补组1蛋白和胸苷酸合成酶的表达
Epidermal Growth Factor Receptor, Excision-Repair Cross-Complementation Group 1 Protein, and Thymidylate Synthase Expression in Penile Cancer.
作者信息
Dorff Tanya B, Schuckman Anne K, Schwartz Rachel, Rashad Sadaf, Bulbul Ajaz, Cai Jie, Pinski Jacek, Ma Yanling, Danenberg Kathleen, Skinner Eila, Quinn David I
机构信息
USC Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA.
USC Keck School of Medicine, Institute of Urology, Los Angeles, CA.
出版信息
Clin Genitourin Cancer. 2016 Oct;14(5):450-456.e1. doi: 10.1016/j.clgc.2016.01.013. Epub 2016 Feb 6.
OBJECTIVE
To describe the expression of tissue epidermal growth factor receptor (EGFR), excision-repair cross-complementation group 1 protein (ERCC1), and thymidylate synthase (TS) in patients with penile cancer and explore their association with stage and outcome.
METHODS
A total of 52 patients with penile squamous cell cancer who were treated at the University of Southern California from 1995 to 2010 were identified. Paraffin-embedded tissue underwent mRNA quantitation and immunohistochemistry for expression of EGFR, ERCC1, and TS. KRAS mutations were evaluated using polymerase chain reaction-based sequencing.
RESULTS
EGFR overexpression was common by mRNA (median, 5.09; range, 1.92-104.5) and immunohistochemistry. EGFR expression > 7 was associated with advanced stage and poor differentiation (P = .01 and .034 respectively) but not with survival in multivariate analysis. ERCC1 mRNA expression was a median of 0.65 (range, 0.21-1.87). TS expression was a median of 1.88 (range, 0.54-6.47). ERCC1 and TS expression were not associated with grade, stage, or survival. There were no KRAS mutations identified. A total of 17 men received chemotherapy; 8 (47%) had an objective response, including 1 with a pathologic complete response. There was a trend for lower expression of EGFR corresponding to a higher likelihood of response (response rate [RR]) to chemotherapy: 67% RR in EGFR mRNA < 7 versus 33% RR in EGFR > 7 (P = .31).
CONCLUSIONS
High expression of EGFR mRNA in squamous cell carcinoma of the penis is associated with advanced stage and poor differentiation, but not survival. In our small heterogeneous subset, molecular marker expression did not show a correlation with the likelihood of chemotherapy response. A prospective evaluation of the role of the EGFR pathway and its regulatory environment in penile cancer is warranted. Given the rarity of this cancer, collaborative prospective cohort evaluations and trials need to be encouraged.
目的
描述阴茎癌患者组织表皮生长因子受体（EGFR）、切除修复交叉互补组1蛋白（ERCC1）和胸苷酸合成酶（TS）的表达情况，并探讨它们与分期及预后的关系。
方法
确定了1995年至2010年在南加州大学接受治疗的52例阴茎鳞状细胞癌患者。对石蜡包埋组织进行mRNA定量分析及免疫组织化学检测，以评估EGFR、ERCC1和TS的表达。采用基于聚合酶链反应的测序法评估KRAS突变情况。
结果
通过mRNA（中位数为5.09；范围为1.92 - 104.5）和免疫组织化学检测发现，EGFR过表达较为常见。EGFR表达>7与晚期及低分化相关（分别为P = 0.01和0.034），但在多因素分析中与生存率无关。ERCC1 mRNA表达中位数为0.65（范围为0.21 - 1.87）。TS表达中位数为1.88（范围为0.54 - 6.47）。ERCC1和TS表达与分级、分期或生存率均无关。未发现KRAS突变。共有17例男性接受了化疗；8例（47%）有客观反应，其中1例为病理完全缓解。EGFR表达降低与化疗反应可能性增加存在一定趋势：EGFR mRNA < 7时反应率（RR）为67%，而EGFR > 7时RR为33%（P = 0.31）。
结论
阴茎鳞状细胞癌中EGFR mRNA高表达与晚期及低分化相关，但与生存率无关。在我们这个小的异质性亚组中，分子标志物表达与化疗反应可能性未显示出相关性。有必要对EGFR通路及其调控环境在阴茎癌中的作用进行前瞻性评估。鉴于这种癌症的罕见性，应鼓励开展协作性前瞻性队列评估和试验。
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