Evidence for Molecular Differences in Prostate Cancer between African American and Caucasian Men
Menée sur des échantillons tumoraux prélevés sur 218 patients atteints d'un cancer de la prostate (105 Africains-Américains et 113 Caucasiens), cette étude compare la fréquence des réarrangements ERG, des délétions PTEN, des surexpressions de SPINK1 et des mutations SPOP entre les deux populations
Purpose: To compare the frequency of ERG rearrangement, PTEN deletion, SPINK1 overexpression, and SPOP mutation in prostate cancer in African American and Caucasian men. Experimental design: Dominant tumor nodules from radical prostatectomy specimens of 105 African American men (AAM) were compared to 113 dominant nodules from Caucasian men (CaM). Clinical and pathologic characteristics of the two groups were similar. SPINK1 overexpression was evaluated by immunohistochemistry, ERG rearrangement and PTEN deletion by FISH, and SPOP mutation by Sanger sequencing. Results: ERG rearrangement was identified in 48/113 tumors (42.5%) in CaM and 29/105 tumors (27.6%) in AAM (p=0.024). PTEN deletion was seen in 19/96 tumors (19.8%) in CaM and 7/101 tumors (6.9%) in AAM (p=0.011). SPINK1 overexpression was present in 9/110 tumors (8.2%) in CaM and 25/105 tumors (23.4%) in AAM (p=0.002). SPOP mutation was identified in 8/78 (10.3%) tumors in CaM and 4/88 (4.5%) tumors in AAM (p=0.230). When adjusted for age, BMI, Gleason score, and pathologic stage, ERG rearrangement and SPINK1 overexpression remain significantly different (p=0.018 and p=0.008, respectively), and differences in PTEN deletion and SPOP mutation approach significance (p=0.061 and p=0.087, respectively). Conclusions: Significant molecular differences exist between prostate cancers in AAM and CaM. SPINK1 overexpression, an alteration associated with more aggressive prostate cancers, was more frequent in AAM, while ERG rearrangement and PTEN deletion were less frequent in this cohort. Further investigation is warranted to determine if these molecular differences explain some of the disparity in incidence and mortality between these two ethnic groups.