High epidermal growth factor receptor immunohistochemical expression in urothelial carcinoma of the bladder is not associated with EGFR mutations in exons 19 and 21: a study using formalin-fixed, paraffin-embedded archival tissues.
High epidermal growth factor receptor immunohistochemical expression in urothelial carcinoma of the bladder is not associated with EGFR mutations in exons 19 and 21: a study using formalin-fixed, paraffin-embedded archival tissues.
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DOI：
10.1016/j.humpath.2011.11.016
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发表时间：
2012-10
期刊：
影响因子：
3.3
通讯作者：
Netto, George J.
中科院分区：
文献类型：
--
作者：
Chaux, Alcides;Cohen, Julie S.;Schultz, Luciana;Albadine, Roula;Jadallah, Sana;Murphy, Kathleen M.;Sharma, Rajni;Schoenberg, Mark P.;Netto, George J.
表皮生长因子受体（EGFR）是erbB酪氨酸激酶家族的成员，据报道在多种实体恶性肿瘤中过表达。在这些肿瘤的一个子集中检测到酪氨酸激酶结构域的外显子19至21的突变，并且其存在与对EGFR抑制剂的更好反应相关。目前正在进行几项临床试验，以评估此类药物在膀胱癌患者中的性能，但EGFR突变状态的数据有限。本研究通过聚合酶链反应评估了19例福尔马林固定、石蜡包埋的膀胱尿路上皮癌组织中EGFR免疫组化表达和外显子19和21突变的存在。将代表性石蜡切片进行显微解剖，使用精确分离系统进行DNA提取。使用单克隆抗EGFR抗体对平行切片进行免疫染色。在任何病例中均未发现EGFR外显子19和21突变。免疫组化EGFR阳性14例。总之，我们发现EGFR蛋白表达在74%的尿路上皮癌，但我们未能检测到EGFR突变的外显子19至21，这表明EGFR的过度表达是不相关的酪氨酸激酶结构域的基因突变的存在。EGFR外显子19和21的突变分析是可行的，从档案组织的显微石蜡切片。EGFR的免疫组化表达可能不能用于预测尿路上皮癌患者对EGFR抑制剂的治疗反应。为了解释EGFR的免疫组化过度表达，在未来的研究中，除了EGFR激酶结构域的突变外，还应研究其他机制。
Epidermal growth factor receptor (EGFR) is a member of the erbB tyrosine kinase family reported to be overexpressed in a variety of solid malignancies. Mutations in exons 19 to 21 of the tyrosine kinase domain have been detected in a subset of these tumors and its presence associated with a better response to EGFR inhibitors. Several clinical trials are currently underway to evaluate the performance of such drugs in patients with bladder cancer, but data on EGFR mutation status are limited. The current study assesses EGFR immunohistochemical expression and the presence of mutations in exons 19 and 21 by polymerase chain reaction in 19 bladder urothelial carcinomas from formalin-fixed, paraffin-embedded tissues. Representative paraffin sections were microdissected for DNA extraction using a pinpoint isolation system. Parallel sections were immunostained using a monoclonal anti-EGFR antibody. No mutations in exons 19 and 21 of EGFR were identified in any of the cases. Immunohistochemical EGFR positivity was observed in 14 of 19 cases. In summary, we found EGFR protein expression in 74% of urothelial carcinomas, but we failed to detect EGFR mutations at exons 19 to 21, suggesting that EGFR overexpression is not related to the presence of mutations in the tyrosine kinase domain of the gene. Mutation analysis of EGFR exons 19 and 21 is feasible in microdissected paraffin sections from archival tissues. Immunohistochemical expression of EGFR may not be useful to predict therapeutic response to EGFR inhibitors in patients with urothelial carcinomas. To explain EGFR immunohistochemical overexpression, other mechanisms besides mutations in the EGFR kinase domain should be investigated in future studies.
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影响因子：
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