The Association of HER-2 Expression with Clinicopathological Characteristics and Clinical Outcomes in Patients with Localized Prostate Cancer After Radical Prostatectomy

<b>Background/Objectives:</b> The purpose of this study was to investigate the association between HER-2 expression and clinicopathological characteristics, biochemical recurrence (BCR) rate, and BCR-free survival in localized prostate cancer (PCa) patients after radical prostatectomy (RP). <b>Methods:</b> Between January 2018 and December 2019, 44 patients with pathologically confirmed localized PCa who underwent RP were included in this study. According to the expressed level of HER-2 protein, patients were divided into four cohorts: cohort-1 (HER-2 0), cohort-2 (HER-2 1+ or 2+), cohort-3 (HER-2 0 or 1+), and cohort-4 (HER-2 2+); the clinicopathological and clinical outcomes were analyzed and compared between cohort-1 and cohort-2, and cohort-3 and cohort-4, respectively. Univariable and multivariable COX regression models and Kaplan-Meier curves were used to determine the association between HER-2 expression and clinicopathological outcomes, including Gleason score (GS), pathological T (pT) stage, positive surgical margins (PSM), and BCR-free survival, respectively. <b>Results:</b> The median follow-up time was 43 months (IQR 35-49). Among the 44 patients, 20 (45.5%) exhibited HER-2 immuno-reactivity, including 14 (31.8%) with HER-2 1+, 6 (13.64%) with HER-2 2+, and 0 (0%) with HER-2 3+ staining. The proportion of patients with PSM was significantly lower in the HER-2 0 group than in those with HER-2 1+ or 2+ (25.0% vs. 65.0%, <i>p</i> = 0.008). Multivariable logistics regression models revealed that HER-2 1+ or 2+ was an independent risk factor that was strongly associated with a higher proportion of PSM (OR, 2.69; 95% CI, 0.62-11.71, <i>p</i> = 0.042). A total of 18 (40.9%) patients experienced BCR after surgery, including 6 (25%) in cohort-1 and 12 (60.0%) in cohort-2 (<i>p</i> = 0.019), as well as 13 (34.2%) in cohort-3 and 5 (83.3%) in cohort-4 (<i>p</i> = 0.023). Kaplan-Meier analysis showed that patients in cohort-1 (HER-2 0) had significantly longer BCR-free survival than those in cohort-2 (HER-2 1+ or 2+) (<i>p</i> < 0.001), and those in cohort-3 had longer BCR-free survival than those in cohort-4 (<i>p</i> < 0.001). Furthermore, patients with PSM showed significantly shorter BCR-free survival compared to those with patients with negative surgical margins (NSM) (<i>p</i> = 0.005). Multivariable Cox regression analysis revealed that HER-2 1+, 2+ (HR, 17.00; 95% CI, 1.38-210.22, <i>p</i> < 0.001), HER-2 2+ (HR, 2.85; 95% CI, 1.23-3.25, <i>p</i> = 0.004), and PSM (HR, 6.12; 95% CI, 3.08-11.72, <i>p</i> = 0.007) were all significant independent predictors of BCR following surgery. <b>Conclusions:</b> HER-2 expression is a common phenomenon in PCa; nearly half of the proportion of localized PCa had HER-2 1+ or 2+, but the cases that expressed HER-2 3+ were rare. Cases with HER-2 1+ or 2+ were more likely to develop BCR compared with HER-2 0. The HER-2 1+ or 2+ expression was closely associated with a higher incidence of PSM and was an independent predictor of shorter BCR-free survival in patients with localized prostate cancer after radical prostatectomy.