βIII-Tubulin Overexpression Is an Independent Predictor of Prostate Cancer Progression Tightly Linked to ERG Fusion Status and PTEN Deletion

Evidence suggests that class III beta-tubulin (beta III-tubulin) may represent a prognostic and predictive molecular marker in prostate cancer. beta III-Tubulin expression was determined by IHC in 8179 prostate cancer specimens in a TMA format. Results were compared with tumor phenotype, biochemical recurrence, v-eta avian erythroblastosis virus E26 oncogene homotog (ERG) status, and deletions on PTEN, 3p13, 5q21, and 6q15. beta III-Tubulin expression was detectable in 25.6% of 8179 interpretable cancers. High beta III-tubulin expression was strongly associated with both TMPRSS2:ERG rearrangement and ERG expression (P < 0.0001 each). High beta III-tubulin expression was tightly Linked to high Gleason grade, advanced pT stage, and early prostate-specific antigen (PSA) recurrence in all cancers (P < 0.0001 each), but also in the subgroups of ERG-negative and ERG-positive cancers. When all tumors were analyzed, the prognostic role of beta III-tubulin expression was independent of Gleason grade, pT stage, pN stage, surgical margin status, and preoperative PSA. Independent prognostic value became even more evident if the analysis was limited to preoperatively available features, such as biopsy specimen Gleason grade, preoperative PSA, cT stage, and beta III-tubulin expression (P < 0.0001 each). beta III-Tubulin expression was associated with PTEN (P < 0.0001) when all tumors were analyzed, but also in the subgroups of ERGnegative and ERG-positive cancers. beta III-Tubulin expression is an independent prognostic parameter. The significant associations with key genomic alterations of prostate cancer, such as TMPRSS2:ERG fusions and PTEN deletions, suggest interactions with several pivotal pathways involved in prostate cancer.