Abstract 1195: A molecular characterization of the anaplastic prostate carcinomas.

Abstract

Abstract Molecular markers that identify clinically meaningful, biologically based, subsets of PC are lacking. This results in inefficient clinical trial designs and suboptimal therapy selection off-protocol. The androgen receptor (AR)-negative small cell PC (SCPC) is an often-unrecognized morphological variant of the disease found on repeat biopsies during the castrate-resistant (CR) progression of PC. Its presence predicts for a poor response to hormonal therapies, a distinct clinical behavior and a short survival. Characteristic clinical features of SCPC are frequently present in patients with CRPC, constituting a clinical syndrome termed anaplastic PC. We hypothesized that the anaplastic PC share underlying biology with SCPC, irrespective of morphology. Preclinical studies show that SCPC are characterized by loss of tumor suppressors and AR signaling, as well as overexpression of mitotic genes and proneural transcription factors. To test our hypothesis we used immunohistochemistry to analyze the expression of markers in these pathways, in tumor biopsies from chemotherapy-naïve men with anaplastic PC participating in a prospective phase II clinical trial. To date we have analyzed 6 markers in 25 samples (6 with pure or mixed SCPC morphology) from prostate biopsies (n=10), transurethral resections of prostate tumors (n=4), bone marrow or bone biopsies (n=9), lymph node (n=1) or brain (n=1). Results are shown in Table 1. Table 1. Immunohistochemistry Anaplastic PC % Positive Cells AR RB1 p53 UBE2C Ki67 CYP17A1 0 8 11 11 5 1 0 < or = 10% 3 6 9 9 8 1 > 10% 14 8 5 11 16 24 Of the 17 samples that had ≤10% RB1+ cells, 10 had ≤10% AR+ cells and 9 had >10% UBE2C+ cells. Of the 11 samples that had ≤10% AR+ cells, 10 also had ≤10% RB1+ cells and 6 had >10% UBE2C+ cells. These data support our hypothesis that the anaplastic prostate carcinomas are characterized by loss of tumor suppressors and overexpression of mitotic genes. Updated results in additional samples and of additional markers will be presented. Citation Format: Ana M. Aparicio, Sankar Maity, Xuemei Wang, Anh G. Hoang, Eleni Efstathiou, Patricia Troncoso, Christopher J. Logothetis. A molecular characterization of the anaplastic prostate carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1195. doi:10.1158/1538-7445.AM2013-1195