Rb, PTEN and p53 Tumor Suppressor Loss Is Common in Prostatic Small Cell Carcinoma.
Hameed Rahimi, Wenle Wang, Nilesh S Gupta, Jonathan I Epstein, George J Netto, Angelo M De Marzo, Tamara L Lotan. Johns Hopkins University School of Medicine, Baltimore, MD; Henry Ford Health System, Detroit, MI
Background: Small cell carcinoma (SCC) of the prostate is a rare subtype with an aggressive clinical course which often occurs with an associated acinar prostatic adenocarcinoma (ACa) component. To date, the frequency of tumor suppressor loss in prostatic SCC has not been extensively studied. Here, we systematically examined expression of retinoblastoma (Rb), PTEN, and p53 proteins by immunohistochemistry (IHC) in prostatic SCC and the associated ACa component.
Design: IHC for Rb, PTEN and p53 was performed on a TMA constructed from 30 cases of prostatic SCC spotted in quadruplicate. 20 cases (66%) were transurethral resections of the prostate (TURP), 8 (27%) were bladder, prostate or rectal biopsies, and 2 (7%) were radical prostatectomies. In 73% (22/30) of cases, a concurrent or prior history of prostatic ACa was established, while 7% (2/30) of cases were diagnosed by positive PSA immunostaining and 7% (2/30) had a documented negative cystoscopy. 23% (7/30) of cases had a concurrent ACa component present on the TMA. Cases were scored for nuclear Rb/p53, and cytoplasmic PTEN using a binary scoring system (+/-). A case was considered to have lost Rb or PTEN protein if any TMA spot showed loss in >95% of tumor cells. Positive p53 expression was scored if any spot in a case showed strong expression (3-4+) in >50% of tumor cells.
Results: 90% (26/29) of SCC cases and 43% (3/7) of concurrent ACa cases showed Rb protein loss. 57% (4/7) of cases showed concordance of the SCC and ACa components for Rb status, while 43% (3/7) showed presence of Rb protein in the ACa component with loss of Rb in the SCC component. 63% (17/27) of SCC cases and 71% (5/7) of concurrent ACa cases had PTEN protein loss. 86% (6/7) of cases showed concordance in SCC and ACa components for PTEN status. 56% (14/25) of SCC cases and 66% (4/6) of concurrent ACa cases showed positive p53 expression. 66% (4/6) of cases showed concordance in the SCC and ACa components for p53 status.
Conclusions: Tumor suppressor loss at the protein level is common in prostatic SCC. Similar to previous studies of lung SCC, we found Rb protein loss in the vast majority of prostatic SCC cases, suggesting that loss of this tumor suppressor is critical to the development of this tumor type in multiple organ systems. Loss of PTEN and expression of p53 were also seen in more than half of prostatic SCC cases. Overall, this data suggests that future therapies targeting these tumor suppressor pathways may be beneficial in the treatment of this aggressive tumor.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 153, Monday Afternoon