title: Androgen-independent prostate cancer is a heterogeneous group of diseases: lessons from a rapid autopsy program.
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 alpha-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.
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA. rajshah@umich.edu
authors.forename: Rajal B
authors.initials: RB
authors.lastname: Shah
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Ronglai
authors.initials: R
authors.lastname: Shen
authors.forename: Debashis
authors.initials: D
authors.lastname: Ghosh
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Gary R
authors.initials: GR
authors.lastname: Macvicar
authors.forename: Soorynarayana
authors.initials: S
authors.lastname: Varambally
authors.forename: Jason
authors.initials: J
authors.lastname: Harwood
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Bismar
authors.forename: Robert
authors.initials: R
authors.lastname: Kim
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000145:classification / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D040081:Protein Array Analysis
chemical_list: D014408:Biomarkers, Tumor