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

Sylvie Clairefond; Véronique Ouellet; Benjamin Péant; Véronique Barrès; Pierre I Karakiewicz; Anne-Marie Mes-Masson; Fred Saad

doi:10.3390/cancers13071688

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

Cancers (Basel). 2021 Apr 2;13(7):1688. doi: 10.3390/cancers13071688.

Authors

Sylvie Clairefond^{1

2}, Véronique Ouellet¹, Benjamin Péant¹, Véronique Barrès¹, Pierre I Karakiewicz^{1

3}, Anne-Marie Mes-Masson^{1

2}, Fred Saad^{1

3}

Affiliations

¹ Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) et Institut du Cancer de Montréal (ICM), Montreal, QC H2X 0A9, Canada.
² Département de Médecine, Faculté de Médecine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
³ Département de Chirurgie, Faculté de Médecine, Université de Montréal, Montreal, QC H3C 3J7, Canada.

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.

Keywords: biochemical recurrence; cancer-specific mortality; development of bone metastases; immunofluorescence; predictive biomarkers; prostate cancer; tumor glands.