Molecular analysis of matched PIN , prostate cancer, and adjacent normal prostate tissue reveals distinct transcriptional signatures and recurrent genomic alterations

Prostate intraepithelial neoplasia (PIN) is a recognized precursor to prostate cancer (PCa) and shares many histological and molecular features with invasive disease. To clarify the relationship between PIN and PCa, we performed integrated genomic and transcriptomic analyses on epithelial and stromal laser-capture microdissected samples in matched PIN (n = 121), PCa (n = 217), and adjacent normal (AN, n = 115) prostate tissue from formalin-fixed paraffin-embedded (FFPE) samples across three datasets. We identified two epithelial and two stromal transcriptomic clusters, termed 'invasive-like' and 'normal-like', which were present across all datasets. Among PIN samples, 46% of epithelial and 38% of stromal samples were classified as invasive-like. Whole-genome sequencing analysis revealed recurrent copy number alterations in PIN and PCa lesions, with recurrent copy number alterations more frequently shared between invasive-like PIN and PCa. This study provides new insight into PIN biology and the relationship between PIN and invasive PCa and highlights a transcriptional signature in PIN samples that may have prognostic implications.