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表皮生长因子受体在阴茎鳞状细胞癌中常过度表达:112 例组织微阵列和数字图像分析研究。

The epidermal growth factor receptor is frequently overexpressed in penile squamous cell carcinomas: a tissue microarray and digital image analysis study of 112 cases.

机构信息

Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 31231, USA; Office of Scientific Research, Norte University, 1614 Asunción, Paraguay.

出版信息

Hum Pathol. 2013 Dec;44(12):2690-5. doi: 10.1016/j.humpath.2013.07.012. Epub 2013 Sep 25.

Abstract

Disseminated penile cancer is usually treated with chemotherapy. However, response rates are far from acceptable. Recently, anti-epidermal growth factor receptor (EGFR) monoclonal antibodies have shown to be clinically useful in penile carcinomas. Nevertheless, only a few cases of penile carcinomas have been evaluated for EGFR expression. In this study, we assessed the immunohistochemical expression of EGFR in 112 patients with penile squamous cell carcinoma. We built 4 tissue microarrays and evaluated EGFR expression using a monoclonal mouse anti-EGFR antibody. For digital image analysis, we used the open-source software ImageJ version 1.47 (NIH, Bethesda, MD) along with the immunomembrane plug-in. Membranous EGFR expression was evaluated, taking into account staining completeness (0-10 points) and staining intensity (0-10 points) for a combined score (0-20 points). We classified the cases as follows: negative EGFR expression, 0 to 3 points; low EGFR expression, 4 to 8 points; and high EGFR expression, 9 to 20 points. The distribution of EGFR immunohistochemical expression was as follows: 13 cases (12%) were EGFR negative, 49 cases (44%) had low EGFR expression, and 50 cases (44%) had high EGFR expression. EGFR expression was not associated with histologic subtype (P = .47), histologic grade (P = .77), or human papillomavirus status (P = .14). In conclusion, immunohistochemical EGFR expression appears to be a common feature of penile carcinomas, independently of histologic subtype, histologic grade, and human papillomavirus presence. Whether or not EGFR expression is associated with EGFR gene mutation or if it can be used to predict response to therapy in patients with disseminated penile cancer should be evaluated in future studies.

摘要

阴茎癌转移通常采用化疗治疗。然而,其反应率远不理想。最近,抗表皮生长因子受体(EGFR)单克隆抗体已被证明对阴茎癌具有临床应用价值。然而,仅有少数阴茎癌病例对 EGFR 表达进行了评估。在这项研究中,我们评估了 112 例阴茎鳞癌患者的 EGFR 免疫组化表达。我们构建了 4 个组织微阵列,并用单克隆鼠抗 EGFR 抗体评估 EGFR 表达。对于数字图像分析,我们使用了开源软件 ImageJ 版本 1.47(NIH,贝塞斯达,MD)以及免疫膜插件。我们考虑了染色完整性(0-10 分)和染色强度(0-10 分),对膜 EGFR 表达进行评估,得出综合评分(0-20 分)。我们将病例分类如下:EGFR 表达阴性,0-3 分;低 EGFR 表达,4-8 分;高 EGFR 表达,9-20 分。EGFR 免疫组化表达的分布如下:13 例(12%)EGFR 阴性,49 例(44%)低 EGFR 表达,50 例(44%)高 EGFR 表达。EGFR 表达与组织学亚型(P=0.47)、组织学分级(P=0.77)或人乳头瘤病毒状态(P=0.14)无关。总之,免疫组化 EGFR 表达似乎是阴茎癌的一个共同特征,与组织学亚型、组织学分级和人乳头瘤病毒的存在无关。在未来的研究中,应评估 EGFR 表达是否与 EGFR 基因突变相关,或者是否可以用于预测转移性阴茎癌患者的治疗反应。

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