Expression of ERBB Family Members as Predictive Markers of Prostate Cancer Progression and Mortality

SIMPLE SUMMARY: Patients diagnosed with prostate cancer are usually offered a standard treatment plan based on their Gleason score, stage, and prostate-specific antigen (PSA) level. However, studies on other cancers have shown the importance of using biomarkers in addition to clinical and pathologic parameters to personalize therapeutic decisions. Given the important heterogeneity in the natural history of localized prostate cancer, novel prognostic biomarkers would aid in patient stratification and decision making. Here, our study shows that members of the ERBB family are markers that have high prognostic value for predicting biochemical relapse, metastasis development, and even prostate cancer-related mortality. The integration of these markers into clinical practice may eventually lead to more appropriate therapeutic decisions in newly diagnosed patients and potentially reduce prostate cancer morbidity and mortality. ABSTRACT: Background: EGFR, ERBB2, ERBB3, and ERBB4 are growth receptors of the ERBB family implicated in the development of epithelial cancers. Studies have suggested a role for EGFR and ERBB3 in the development of prostate cancer (PC), while the involvement of ERBB2 and ERBB4 remains unclear. In this study, we evaluated the expression of all members of the ERBB family in PC tissue from a large cohort and determined their contribution, alone or in combination, as prognostic markers. Methods: Using immunofluorescence coupled with digital image analyses, we quantified the expression of EGFR, ERBB2, ERBB3, and ERBB4 on radical prostatectomy specimens (n = 285) arrayed on six tissue microarrays. By combining EGFR, ERBB2, and ERBB3 protein expression in a decision tree model, we identified an association with biochemical recurrence (log rank = 25.295, p < 0.001), development of bone metastases (log rank = 23.228, p < 0.001), and cancer-specific mortality (log rank = 24.586, p < 0.001). Conclusions: Our study revealed that specific protein expression patterns of ERBB family members are associated with an increased risk of PC progression and mortality.