Cell Type-Specific Biomarkers To Predict the Risk of Prostate Cancer in Men with Increased PSA but Negative Biopsies
Susan Kerkoutian, Yin Sun, Xinmin Li, Jason Scapa, Jiaoti Huang. UCLA David Geffen School of Medicine, Los Angeles, CA
Background: About 75% of men with elevated PSA have negative prostate biopsies. Among them, many have benign conditions while some have prostate cancer (PCa) missed by biopsy. Since these possibilities cannot be easily distinguished, all men are offered close followup including re-biopsies, resulting in unnecessary anxiety, discomfort and expenses for many with no risk of PCa. Biomarkers are urgently needed to stratify these patients into different risk groups. Since benign biopsies are from either normal prostates (no PCa) or PCa-adjacent prostates, we attempted to identify genes differentially expressed between the two tissue types.
Design: Fresh PCa-adjacent benign prostates (n=10) were procured from prostatectomies and confirmed by frozen section diagnosis. Normal prostates (n=10) were procured from simple prostatectomies (for BPH) or cystoprostatectomies (for bladder cancer) without incidental PCa. Single cell suspensions of fresh epithelial cells were prepared by digestion of tissue in a collagenase-based solution. Fluorescence-activated cell sorting (FACS) based on cell surface markers was used to obtain basal (Trop2+CD49fhigh) and luminal (Trop2+CD49flow) cells as reported (Nat Protoc, 6:656). Cancer cells were purified based on luminal markers. RNA was isolated and microarray analysis performed to compare gene expression profiles.
Results: 1). Gene expression profiles are similar within same epithelial cell types (basal or luminal); 2). Luminal and basal cells have different gene expression profiles; 3). PCa-adjacent basal cells have different gene expression profiles from those from normal prostates; 4). PCa-adjacent luminal cells have gene expression profile similar to PCa cells but different from normal luminal cells; 5). Statistical analysis identified many cell-type (basal or luminal)-specific genes differentially expressed between PCa-adjacent prostates and normal prostates.
Conclusions: 1). Comparing gene expression using purified cell populations uncovered biomarkers that would be missed if tissue chunks were used; 2). Luminal cells adjacent to PCa are molecularly similar to cancer cells, suggesting field effects; 3). Many cell type-specific genes are differentially expressed between PCa-adjacent prostate and normal prostate, and may serve as biomarkers to distinguish the two tissue types; 4). The biomarkers may be used to predict the risks of having PCa in men with elevated PSA but negative biopsies. Men with low risks can be spared repeated invasive procedures while those with high risks can be re-biopsied early to identify undiagnosed cancer.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 135, Monday Morning