Prevalence of ERG Rearrangement, SPINK1 Overexpression and PTEN Deletion in Prostate Cancer of Korean Men
Ghil Suk Yoon, Kyung Park, Theresa MacDonald, Jae Young Choi, Zhengming Chen, Mark A Rubin, Juan Miguel Mosquera. Kyungpook National University, Daegu, Korea; Weill Medical College of Cornell University, New York, NY
Background: It is well documented that the prevalence of prostate cancer (PCA) in Asian men is lower than that of Caucasian men; however, risk factors and molecular mechanisms behind this difference have not been fully elucidated. In this study, we investigated some molecular events occurring in PCA of Korean men and searched for any significance in their clinical presentation.
Design: 122 robotic-assisted laparoscopic prostatectomy specimens from a single academic institution in South Korea represented in tissue microarrays were studied. ERG and SPINK1 expression was evaluated by immunohistochemistry, and ERG rearrangement and PTEN deletion was assessed by fluorescence in situ hybridization. Results were correlated with clinical parameters including age, pre-biopsy PSA, tumor grade and stage, surgical margin status, lymphovascular invasion, and biochemical recurrence.
Results: ERG gene fusion was present in 35% (42/119 - 51% with translocation through deletion, 49% with translocation through insertion), SPINK1 overexpression in 7% (8/109), and PTEN deletion (all hemizygous) in 16% (15/93) of assessable cases. Age at diagnosis ranged from 50 to 76 (median 67 years) and PSA ranged from 3.3 to 286.8 ng/mL (median 10.6 ng/mL). Twelve (9.8%) subjects had PCA Gleason 6, 68 (55.7%) had Gleason 7, 12 (9.8%) had Gleason 8, 13 had Gleason 9 (10.7%) and 1 (0.8%) had Gleason 10 tumors. Pathological stage in 43 (35%) cases was pT2, 47 (39%) had pT3a disease, and 32 (26%) had pT3b. Surgical margins were positive in 63 (52%) specimens, and lymphovascular invasion was identified in 18 (15%). Biochemical recurrence occurred in 22 (18%) patients. In addition to surgery, 16 patients received hormone therapy. There was no significant association between these molecular alterations and clinical parameters. It was five times more likely for ERG-negative tumors to be PTEN wild type compared to ERG-positive PCA in this cohort (p=0.009). Among 83 patients with ERG, SPINK1, and PTEN data available, 38 (46%) had PCA that was negative for all three molecular biomarkers.
Conclusions: The frequency of ERG rearrangement, SPINK1 overexpression, and PTEN deletion in Korean men with PCA is comparable to those previously reported in Caucasian cohorts. Many Korean men are not routinely PSA screened and present with symptoms at time of diagnosis. This late detection could explain high PSA levels at diagnosis and higher pathological tumor stage and grade. This study also confirms the significant association between ERG fusion and loss of PTEN.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 176, Tuesday Afternoon