Androgen-Independent Prostate Cancer Is a Heterogeneous Group of Diseases

TLDR

Prostate cancer metastasis biology has been constrained by limited tissue availability, and recognizing its heterogeneity is essential for developing diagnostic, prognostic, and therapeutic strategies. The study aimed to analyze clinical data, distribution, morphology, immunophenotypes, and gene expression from 30 rapid autopsies of men with hormone‑refractory prostate cancer. Researchers constructed a tissue microarray of the autopsy samples, quantified expression of PSA, AR, chromogranin, synaptophysin, MIB‑1, and AMACR, performed hierarchical clustering of 16 tumors to link cDNA patterns with morphology, and compared results across and within patients. The results revealed that metastatic hormone‑refractory prostate cancer exhibits heterogeneous morphology, immunophenotype, and genotype, indicating that metastatic disease comprises multiple distinct disease entities even within a single patient.

Abstract

Abstract Understanding the biology of prostate cancer metastasis has been limited by the lack of tissue for study. We studied the clinical data, distribution of prostate cancer involvement, morphology, immunophenotypes, and gene expression from 30 rapid autopsies of men who died of hormone-refractory prostate cancer. A tissue microarray was constructed and quantitatively evaluated for expression of prostate-specific antigen, androgen receptor, chromogranin, synaptophysin, MIB-1, and α-methylacylCoA-racemase markers. Hierarchical clustering of 16 rapid autopsy tumor samples was performed to evaluate the cDNA expression pattern associated with the morphology. Comparisons were made between patients as well as within the same patient. Metastatic hormone-refractory prostate cancer has a heterogeneous morphology, immunophenotype, and genotype, demonstrating that “metastatic disease” is a group of diseases even within the same patient. An appreciation of this heterogeneity is critical to evaluating diagnostic and prognostic biomarkers as well as to designing therapeutic targets for advanced disease.