MMSET Is Associated with Prostate Cancer Progression and Over-Expressed in Androgen Independent Metastatic Prostate Cancer.
Rohit Mehra, Irfan Asangani, Robert Lonigro, Xuhong Cao, Neena E Philips, Khalid Suleman, Sooryanarayana Varambally, Mark A Rubin, Rajal B Shah, Kenneth J Pienta, Arul M Chinnaiyan. University of Michigan, Ann Arbor; Weill Cornell Medical College, New York; Caris Life Sciences, Irving
Background: MMSET has been extensively studied in several tumors and is known to be part of the recurrent t(4;14) (p16;q32) translocation in Multiple Myeloma. We sought to characterize MMSET in a cohort of benign prostate tissues, clinically localized prostate cancer (PCA) and a warm autopsy cohort of androgen independent lethal metastatic PCAs and investigate its correlation with prostate cancer progression and the clinical features of these patients.
Design: MMSET mRNA levels in prostate cancer datasets were obtained using Oncomine, a cancer microarray database (www.oncomine.org). A tissue microarray (TMA) was constructed representing 96 patients with clinically localized prostate cancers who underwent radical prostatectomy at the University of Michigan as the primary monotherapy. Two other tissue microarrays (TMAs) were constructed representing 156 tumor foci (metastatic PCA samples and primary PCA, when present) from 47 rapid autopsies of men died of androgen independent metastatic PCA. Immunohistochemical analysis was performed using antibodies against MMSET on these tissue microarrays.
Results: Meta-analysis using cDNA datasets in Oncomine revealed MMSET to be overexpressed in metastatic prostate cancer compared to benign and clinically localized prostate cancer (Varamally et al and Lapointe et al). Immunohistochemical evaluation and analysis of TMAs revealed MMSET to be over-expressed in clinically localized prostate cancer compared to benign prostate tissues and this difference was statistically significant (p = 0.0004). MMSET was further over-expressed in androgen independent metastatic prostate cancer compared to clinically localized prostate cancer. Further survival analysis is being carried out to investigate the role of MMSET in prostate cancer outcome.
Conclusions: Here we show the MMSET to be highly expressed in prostate cancer. Our results suggest that MMSET expression increases during the natural history of prostate cancer progression, in particular with androgen-independent state and metastatic disease. It underscores the importance of investigating the functional role of MMSET in prostate cancer and its usefulness as a potential therapeutic target of cancer therapy.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 66, Wednesday Morning