Decreased Expression of CD38 in High Grade Prostate Cancer
JL Schmidt, AT Johnson (co-first author), SC Schmechel. University of Minnesota, Minneapolis, MN
Background: Prostatic adenocarcinoma (PCa) is the most frequently diagnosed cancer of men. Although most men with PCa have an indolent course, some tumors behave aggressively. Methods to identify potentially lethal PCa represent a major challenge, particularly based on small biopsy samples. Tumor grade is prognostically important, but substantial differences have been observed between grades assigned on biopsies versus subsequent prostatectomies. Grade-selective immunohistochemical markers may improve grading and allow identification of aggressive PCa. We used microarray data mining and tissue microarray (TMA) methods to identify and validate the grade-selective marker CD38.
Design: Using microarray RNA expression datasets, we identified genes whose RNA expression patterns distinguished Gleason pattern 3 from high grade (HG; Gleason patterns 4 and 5) patterns. CD38 was down-regulated in HG PCa, whereas prostate specific membrane antigen (PSMA) was up-regulated in HG PCa. TMAs were made from 48 prostatectomy specimens, with 40, 36, and 5 areas of pattern 3, 4, and 5, respectively. Commercial antibodies and 3,3-diaminobenzidine (DAB) were used to evaluate CD38 and PSMA expression. Immunostained slides were scanned and DAB staining intensity/area of PCa glands was determined using Aperio slide digitalization and computer-assisted techniques. P-values were derived from t-tests.
Results: CD38 expression was decreased in HG PCa. The mean expression was 23.3(standard error[SE]=5.2), 18.1(SE=4.9), and 4.5(SE=2.6) in patterns 3, 4 and 5, respectively. The expression in patterns 3 and 5 was significantly different(p=0.002). There was a trend toward higher PSMA expression in HG PCa. The mean expression was 35.2(SE=5.3), 45.9(SE=4.8), and 57.9(SE=5.4) in patterns 3, 4 and 5, respectively. CD38 has been shown to induce apoptosis in B-cell precursors. Decreased CD38 expression has been observed in proliferative prostate tissues including fetal prostate, benign prostatic hyperplasia and PCa. Our finding that CD38 expression is significantly decreased in HG PCa has not been reported previously to our knowledge. Together, these data suggest that HG PCa may have a proliferative advantage due to decreased CD38 expression and resultant decreased tumor cell apoptosis.
Conclusions: CD38 expression is significantly decreased in HG PCa. Diminished CD38 expression may result in decreased apoptotic activity and increased aggressiveness in HG PCa. Additional studies may address the potential utility of CD38 or other grade-selective markers in improving biopsy grading.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 135, Monday Morning