The George Washington University School of Medicine and Health Sciences, Washington, DC, USA; The Edward P. Evans Precision Oncology Center of Excellence, Washington DC VA Medical Center, Washington, DC, USA.
Institute for Clinical Research, Washington, DC, USA.
Ann Diagn Pathol. 2023 Dec;67:152219. doi: 10.1016/j.anndiagpath.2023.152219. Epub 2023 Oct 20.
Abnormalities in HER2 are well-established oncogenic drivers and are approved therapeutic targets in various malignancies. Prior studies evaluating HER2 expression in prostate cancer (PCa) have yielded variable results. Most of these studies used immunohistochemistry scoring systems based on breast cancer data. The goal of this study was to determine the prevalence and clinical significance of HER2 expression using a scoring system that better reflects the HER2 staining pattern observed in PCa.
We randomly selected similar numbers of localized low risk (AJCC stage I), locally advanced (AJCC stages II & III), and metastatic (AJCC stage IV) PCa patients treated at the DC VA Medical Center between 2000 and 2022. Among them, we included patients who had sufficient PCa tissue samples and clinical information required for this analysis. Two experienced pathologists independently scored HER2 expression (Ventana Pathway anti-HER2) according to a modified gastric cancer HER2 scoring system.
Out of the 231 patients included, 85 % self-identified as Black. 58.9 % of patients expressed HER2 (1+: 35.5 %; 2+: 18.2 %; 3+: 5.2 %). Validity of the results was confirmed using the HercepTest antibody. Higher HER2 expression was associated with a higher Gleason Score/Grade Group and advanced disease.
Our findings support the adverse prognostic impact on HER2 in PCa. We propose the use of a modified scoring system to evaluate HER2 expression in PCa. The observed high prevalence of HER2 expression supports the consideration of novel HER2-targeted therapies addressing even low levels of HER2 expression in future PCa trials.
HER2 异常是明确的致癌驱动因素，并且是多种恶性肿瘤的批准治疗靶点。先前评估前列腺癌（PCa）中 HER2 表达的研究得出了不同的结果。这些研究大多使用基于乳腺癌数据的免疫组织化学评分系统。本研究的目的是使用更好地反映在 PCa 中观察到的 HER2 染色模式的评分系统来确定 HER2 表达的流行率和临床意义。
我们随机选择了数量相似的在 2000 年至 2022 年期间在 DC VA 医疗中心治疗的局限性低危（AJCC 分期 I）、局部进展性（AJCC 分期 II 和 III）和转移性（AJCC 分期 IV）PCa 患者。其中，我们纳入了有足够的 PCa 组织样本和进行此项分析所需的临床信息的患者。两名经验丰富的病理学家根据改良的胃癌 HER2 评分系统独立对 HER2 表达（Ventana 通路抗 HER2）进行评分。
在纳入的 231 名患者中，85%自我认定为黑人。58.9%的患者表达 HER2（1+：35.5%；2+：18.2%；3+：5.2%）。使用 HercepTest 抗体验证了结果的有效性。更高的 HER2 表达与更高的 Gleason 评分/分级组和更晚期疾病相关。
我们的研究结果支持 HER2 在 PCa 中的不良预后影响。我们建议使用改良的评分系统来评估 PCa 中的 HER2 表达。观察到的 HER2 表达高患病率支持在未来的 PCa 试验中考虑针对甚至低水平 HER2 表达的新型 HER2 靶向治疗。
