Institute of Pathology, Department of Urology, Prostate Cancer Center University Medical Center, Hamburg-Eppendorf, Germany.
Clin Cancer Res. 2010 Mar 1;16(5):1553-60. doi: 10.1158/1078-0432.CCR-09-2546. Epub 2010 Feb 23.
The HER2 oncogene is involved in the biology of many different tumor types and serves as a prognostic marker and a therapeutic target in breast cancer. In contrast to breast cancer, studies on Her2 overexpression and gene amplification in prostate cancer have yielded different results. The purpose of this study was to learn more on the prevalence and clinical significance of HER2 amplification and overexpression in prostate cancer.
A tissue microarray containing >2,000 prostate cancers with follow-up data was used. Tissue microarray sections were analyzed on protein and DNA level using two different antibodies (HercepTest, DAKO; Novocastra NCL-CB11) and fluorescence in situ hybridization.
Immunohistochemical analyses showed highly similar results for both antibodies. Detectable Her2 immunostaining was observed in 17.2% for the HercepTest and in 22.5% for the Novocastra antibody with the vast majority of cases showing 1+ or 2+ staining. For both antibodies (HercepTest/Novocastra), significant associations were found between positive staining and high Gleason grade (P < 0.0001, both), advanced pT stage (P < 0.0001/P = 0.0015), rapid tumor cell proliferation (P = 0.0004/P = 0.0071), and tumor recurrence (P < 0.0001, both). HER2 amplification was only found in 1 of 2,525 analyzable cases (0.04%).
Low-level Her2 overexpression occurs at relevant frequency in prostate cancer and in the absence of gene amplification. Increased Her2 expression may potentially lead to an aggressive behavior of tumor cells through the stimulation of tumor cell proliferation because Her2 staining was shown to be significantly associated with Ki67 labeling index. These data argue for reconsidering anti-Her2 therapy, possibly with modified approaches.
HER2 癌基因参与多种不同肿瘤类型的生物学过程，是乳腺癌的预后标志物和治疗靶点。与乳腺癌不同，针对前列腺癌中 Her2 过表达和基因扩增的研究结果不同。本研究旨在进一步了解前列腺癌中 HER2 扩增和过表达的流行率和临床意义。
使用包含 >2000 例前列腺癌和随访数据的组织微阵列。使用两种不同的抗体（HercepTest，DAKO；Novocastra NCL-CB11）和荧光原位杂交技术在蛋白质和 DNA 水平上分析组织微阵列切片。
两种抗体的免疫组织化学分析结果高度相似。HercepTest 检测到的可检测 Her2 免疫染色率为 17.2%，Novocastra 抗体为 22.5%，绝大多数病例显示 1+或 2+染色。对于两种抗体（HercepTest/Novocastra），阳性染色与高 Gleason 分级（P<0.0001，均）、高级 pT 分期（P<0.0001/P=0.0015）、快速肿瘤细胞增殖（P=0.0004/P=0.0071）和肿瘤复发（P<0.0001，均）显著相关。在 2525 例可分析病例中仅发现 1 例（0.04%）存在 HER2 扩增。
低水平的 Her2 过表达在前列腺癌中以相关频率发生，且不存在基因扩增。由于 Her2 染色与 Ki67 标记指数显著相关，因此表达增加可能潜在导致肿瘤细胞的侵袭性行为。这些数据表明需要重新考虑抗 Her2 治疗，可能需要采用改良方法。
