Correlation of Immunohistochemical Expression of Protein-Coding Genes RAD23B, SIM2S, Notch3, BID and FBP with Biochemical Recurrence in Patients Following Radical Prostatectomy for Prostatic Adenocarcinoma
Carlos S Moreno, Soma Sannigrahi, Jessica Cheng, Wei Zhou, John A Petros, Theresa W Gillespie, Adeboye O Osunkoya. Emory University School of Medicine, Atlanta
Background: One of the challenges in prostate cancer research is the development of effective predictors of tumor recurrence following radical prostatectomy, to determine whether immediate adjuvant therapy is warranted. This is even more important in patients who have negative margins and may be lost to follow up. To date very few biomarkers have been identified that accurately predict the possibility of tumor recurrence or biochemical failure in this setting.
Design: A panel of five biomarkers (RAD23B, SIM2S, Notch3, BID and FBP) were selected based on cDNA-mediated Annealing, Selection, extension and Ligation (DASL) assay. A TMA was constructed from 94 radical prostatectomy cases with available detailed follow-up data. Five TMA sections were stained with antibodies to RAD23B, SIM2S, Notch3, BID, and FBP. Intensity of the various immunohistochemical stains were scored blindly as follows; 0-negative, 1+ (weak), 2+ (intermediate) and 3+ (strong). The expression of these markers was correlated with biochemical recurrence (BCR) using Fisher's exact test with samples divided into categories 0-2+ vs. 3+ for staining and positive vs. negative for BCR.
Results: Median patient age was 64 yrs (range 47-74yrs). Median Pre-operative PSA was 6.6 (range 1.6-72.6). Gleason scores were as follows: 12/97 cases (3+3=6), 53/97 cases (3+4=7), 23/97 cases (4+3=7), 7/97 cases (4+4=8), 1/97 cases (4+5=9), and 1/97 cases (5+4=9). There were 59 Caucasian and 31 African-American cases, with the remaining 7 of unknown race. There were 61/97 cases without BCR and 34/97 cases with BCR. Increased expression of RAD23B (p = 0.023) and SIM2S (p = 0.021) demonstrated statistical significance by Fisher's exact test for discriminating between patients with BCR and those without BCR. Expression of BID (two-tailed p-value = 0.357), NOTCH3 (p = 0.237), and FBP (p = 0.237) did not demonstrate statistical significance between patients with BCR and those without BCR. Interestingly, there was no statistically significant correlation between any of the markers and pathologic stage, Gleason score, patient race, or pre-operative PSA levels.
Conclusions: RAD23B and SIM2S may be useful immunohistochemical biomarkers in the prediction of BCR in patients following radical prostatectomy, irrespective of pathologic stage, Gleason score, patient race, or pre-operative PSA levels. Patients with tumors that demonstrate increased expression of these markers may benefit from close follow-up after radical prostatectomy.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 121, Wednesday Morning