Expression of ERBB Family Members as Predictive Markers of Prostate Cancer Progression 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.

Transcriptomic Signature and Growth Factor Regulation of Castration-Tolerant Prostate Luminal Progenitor Cells

“…The EGFR/ERBB4, MET and IGF-1R families of growth factor receptor have been implicated in prostate cancer [ 31 , 68 , 69 ]. Receptors of the EGFR/ERBB family are tightly correlated with poor prognosis, drug resistance, cancer metastasis, and lower survival rate of prostate cancer patients [ 68 , 70 ]. Overexpression of ligands and/or receptors of ERBB and MET pathways has been reported in prostate cancer [ 69 , 71 , 72 ].…”

Whole-exome sequencing reveals a comprehensive germline mutation landscape and identifies twelve novel predisposition genes in Chinese prostate cancer patients

“…Protein-protein interaction networks analysis of deleterious genes and the VUS-containing genes in the PI3K-Akt signaling pathway revealed that these two groups of genes interacted closely with each other in both cohorts by the nodes of ERBB family (EGFR, ERBB2 and ERBB3), BRCA1, HRAS, and TP53. A recent study revealed that the combined protein expression patterns of EGFR, ERBB2, and ERBB3 were associated with a higher risk of progression and mortality in prostate cancer [ 72 ]. HRAS, as one of the Ras oncogene family, was found to have increased amplification rate in hormone-resistant prostate cancer compared with hormone-sensitive prostate cancer [ 73 ].…”

High Keratin-7 Expression in Benign Peri-Tumoral Prostatic Glands Is Predictive of Bone Metastasis Onset and Prostate Cancer-Specific Mortality

“…The prognostic value of KRT7 expression was assessed in a cohort of radical prostatectomy specimens ( n = 285 patients) from well-balanced localized PC with clinical/ pathological characteristics detailed in Supplementary Table S1 [ 24 , 25 ]. The incidence of biochemical recurrence (BCR) at 5 years was 33% (94 patients), and 9.8% (28 patients) of the cohort had an onset of bone metastasis leading in 6.3% of cases (18 patients) to a prostate-cancer specific death.…”

“…This TF123 was composed of a total of six TMA blocks. For each patient, 2 adjacent benign duplicate 0.6 mm cores and 2 tumoral duplicate cores were available, as previously published [ 24 , 25 ]. The composition of the cohort is described in Supplementary Table S1 .…”

“…Data pre-processing was performed with quality control of the tissue cores as described previously [ 24 , 25 ]. To accurately compare all of the TMAs (6 separate blocks), an MFI normalization was performed to compensate for the observed differences related to slide scanning and imaging in the average fluorescence intensity between each slide arising from the 6 blocks.…”