Login to Access Video or Poster Abstract: MP87-11
Sources of Funding: DOD PC131996, PCF-Movember GAP1 Unique TMAs Project, Prostate Cancer Foundation (PCF) Creativity Award, Jean Perkins Foundation, NIH/NCI P01 CA098912-09, NIH R01CA131255 and P50CA092131, Stephen Spielberg Team Science Award._x000D_ _x000D_

Introduction

We recently identified and validated 3 intrinsic prostate cancer subtypes (PCS) based on a 37-gene expression signature. To evaluate the PCS system as a prognostic tool, we determined the frequencies of PC subtypes in diagnostic prostate needle biopsies (PNBX) collected from men with high-grade localized PC (clinical stage M0) who remained disease-free or progressed to castration-resistant prostate cancer (CRPC) after definitive treatment as well as in PNBX of men who were newly diagnosed with metastatic disease (clinical stage M1).

Methods

PNBX cases were selected from a cohort of 486 patients with high-grade localized or metastatic prostate cancer (mPC), diagnosed and treated in the Greater Los Angeles VA Healthcare System between 2000 and 2015. RNA sequencing (RNAseq) was performed on 86 tumor foci from 68 formalin-fixed, paraffin-embedded (FFPE) PNBXs: thirty nine cases with de novo metastases (M1), 6 cases who progressed to metastasis (M0-P), and 23 PC cases without progression (M0-NP). Computation of pathway activation profiles, principal component analysis, and application of the 37-gene PCS classifier were performed for assignment of subgroups. The results of this analysis were compared to publically available datasets (PCF and SU2C datasets) of primary PC and CRPC metastases.

Results

Importantly, analysis of RNAseq data revealed adequate levels of transcriptome coverage (>18,000 genes) in all 68 cases. Significant differences in survival were observed in M1 cases compared to M0-P and M0-NP. The frequency of PCS groups in PNBX specimens of patients with M1 stage (36% PCS1; 21% PCS2; 44% PCS3) was similar to that of biopsies from metastatic CRPC in the PCF and SU2C cohort (35% PCS1; 20% PCS2; 45% PCS3). A high proportion of the poor prognosis PCS1 (n=14 of 15 cases) was identified in PNBX of patients with M1 stage compared to M0 stage.

Conclusions

Although the subtyping of PNBX and derived staging and prognostic information warrants further confirmation in a larger cohort, the data demonstrate a promising potential for a footprint of concurrent or future metastatic disease in PNBXs obtained at the time of PC diagnosis.

Funding

DOD PC131996, PCF-Movember GAP1 Unique TMAs Project, Prostate Cancer Foundation (PCF) Creativity Award, Jean Perkins Foundation, NIH/NCI P01 CA098912-09, NIH R01CA131255 and P50CA092131, Stephen Spielberg Team Science Award._x000D_ _x000D_