SUPPLEMENTARY TABLE 1. AVPC ('ANAPLASTIC') ELIGIBILITY CRITERIA FOR NCT00514540, A PHASE II STUDY OF CARBOPLATIN AND DOCETAXEL IN PATIENTS WITH ANAPLASTIC PROSTATE CARCINOMA. SUPPLEMENTARY TABLE 2. CLINICOPATHOLOGICAL FEATURES OF THE PDX DONOR PATIENTS. SUPPLEMENTARY TABLE 3. PDX GROWTH RATE AND PSA PRODUCTION. SUPPLEMENTARY TABLE 4. ANTIBODIES USED FOR IMMUNOHISTOCHEMISTRY AND WESTERN BLOT. SUPPLEMENTARY TABLE 5. qRT-PCR PRIMER SEQUENCES. SUPPLEMENTARY TABLE 6. DONOR PATIENT CHARACTERISTICS. SUPPLEMENTARY TABLE 7. SERUM MARKER LEVELS AT TIME OF REGISTRATION TO NCT00514540. SUPPLEMENTARY TABLE 8. PRINCIPAL COMPONENT VARIATE WEIGHTINGS TCGA/UNSELECTED CRPC/AVPC SAMPLES. SUPPLEMENTARY TABLE 9. LINEAR DISCRIMINANT ANALYSIS WEIGHTS. SUPPLEMENTARY TABLE 10. Tp53 MUTATIONS DETECTED IN TCGA, UNSELECTED CRPC (21) AND AVPC SAMPLES.
Funding
NIH/NCI
the Prostate Cancer Foundation, the Joan Stanford Alexander Family Fund, the Michael and Susan Dell Foundation (honoring Lorraine Dell), and The University of Texas MD Anderson Prostate Cancer Moon Shot Program
ARTICLE ABSTRACT
Purpose: Morphologically heterogeneous prostate cancers that behave clinically like small-cell prostate cancers (SCPC) share their chemotherapy responsiveness. We asked whether these clinically defined, morphologically diverse, “aggressive variant prostate cancer (AVPC)” also share molecular features with SCPC.Experimental Design: Fifty-nine prostate cancer samples from 40 clinical trial participants meeting AVPC criteria, and 8 patient-tumor derived xenografts (PDX) from 6 of them, were stained for markers aberrantly expressed in SCPC. DNA from 36 and 8 PDX was analyzed by Oncoscan for copy number gains (CNG) and losses (CNL). We used the AVPC PDX to expand observations and referenced publicly available datasets to arrive at a candidate molecular signature for the AVPC.Results: Irrespective of morphology, Ki67 and Tp53 stained ≥10% cells in 80% and 41% of samples, respectively. RB1 stained <10% cells in 61% of samples and AR in 36%. MYC (surrogate for 8q) CNG and RB1 CNL showed in 54% of 44 samples each and PTEN CNL in 48%. All but 1 of 8 PDX bore Tp53 missense mutations. RB1 CNL was the strongest discriminator between unselected castration-resistant prostate cancer (CRPC) and the AVPC. Combined alterations in RB1, Tp53, and/or PTEN were more frequent in the AVPC than in unselected CRPC and in The Cancer Genome Atlas samples.Conclusions: Clinically defined AVPC share molecular features with SCPC and are characterized by combined alterations in RB1, Tp53, and/or PTEN. Clin Cancer Res; 22(6); 1520–30. ©2015 AACR.
