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[Cancer Research 64, 9209-9216, December 15, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Androgen-Independent Prostate Cancer Is a Heterogeneous Group of Diseases

Lessons from a Rapid Autopsy Program

Rajal B. Shah1,3, Rohit Mehra1, Arul M. Chinnaiyan1,3, Ronglai Shen4, Debashis Ghosh4, Ming Zhou1, Gary R. MacVicar2, Soorynarayana Varambally1, Jason Harwood1, Tarek A. Bismar5, Robert Kim5, Mark A. Rubin5,6,7 and Kenneth J. Pienta2,3

Departments of 1 Pathology, 2 Medical Oncology, 3 Urology, and 4 Biostatistics, University of Michigan School of Medicine, Ann Arbor, Michigan; 5 Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts; 6 Department of Pathology, Dana Farber Cancer Institute, Boston, Massachusetts; and 7 Department of Pathology, Harvard Medical School, Boston, Massachusetts

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.




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