Human Epidermal Growth Factor Receptor 2 Expression in Prostatic Carcinomas: A Systematic Review and Meta‐Analysis of a Potential Therapeutic Target

ABSTRACT Introduction The clinical relevance of HER2 expression profile in solid cancers has expanded with the evolving landscape of HER2 targeting agents. This systematic review and meta‐analysis aim to detail the prevalence of HER (over)expression in prostate cancer and identify patient/disease subgroups with enriched HER2 overexpression. Methods Literature searches of five databases were performed. HER2 scores with cross‐tabulation of clinicopathological parameters were extracted for pooled prevalence and odds ratio analyses. Study quality, heterogeneity, and publication bias were assessed by the CASP checklist, I 2 index, and LFK index. Results In total, 16 studies were included with 1258 cases. There were 669 (53.18%), 269 (21.38%), 250 (19.87%), and 70 (5.56%) of HER2 Scores 0/1/2/3, respectively. Pooled analysis indicated a prevalence of 4.9% (95% CI 3.0%–7.2%) for HER2 Score 3 and 42.0% (95% CI 29.0%–55.6%) for HER2 non‐negative (Scores 1–3). Subgroup analysis comparing HER2 negative (0, 1) and HER2 overexpression (3) indicated higher Gleason score (OR = 0.061, 95% CI: 0.010–0.359, p < 0.001), higher disease stage (OR = 0.063, 95% CI: 0.016–0.252, p < 0.001) and biopsies from metastatic site (OR: > 100, 95% C.I.: > 100–> 100, p < 0.001) favoring HER overexpression, without significant differences for patient age or prostate‐specific antigen (PSA) level. I 2 was 91.63% with meta‐regression analysis showing study quality as a source of heterogeneity ( p = 0.043). LFK index was 1.93 (moderate publication bias risk, p = 0.054). Conclusions HER2 overexpression is rare in prostatic carcinomas but nearly half show HER2 expression of Score 1 or above. Cases with higher Gleason score and advanced disease stage are more likely to overexpress HER2.