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[822] TMPRSS 2: A Prostate Cancer Marker of Metastasis and a Potential Molecular Target for Therapy

LD True, J Lucas, S Hawley, M Matsumoro, B Knudsen, R Etzioni, PS Nelson. University of Washington, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA

Background: The fusion of the TMPRSS2 promoter with members of the ets family of growth factors has been implicated as an important event in the development of prostate cancer. Given the importance of the TMPRSS2 in the development and progression of prostate cancer, we studied expression of this gene product in primary and metastatic prostate cancer.
Design: We made a monoclonal antibody to a peptide in the extracellular domain of the TMPRSS2 gene product. Specificity was assessed by Western blot and blocking immunohistochemical stains. Using tissue microarrays representing a spectrum of grades and stages of 100 primary prostate cancers and of 20 metastatic prostate cancer samples, we characterized expression of TMPRSS2 using an indirect immunoperoxidase method. An additional TMA included tissue from 50 patients treated with 2 doses of 5- reductase inhibitor dutasteride (0.5 mg and 3.5 mg). Stains were evaluated on a 4-point scale (absent, equivocal, present in a minority of cells, present in a majority of cells). Statistical evaluation used logistic expression analysis addressing the hypotheses that cancer cells stain more than normal cells, that staining differs by grade, and that metastases stain more than primary tumor cells.
Results: TMPRSS 2 is overexpressed more in prostate cancer compared with normal prostate cells and more in metastases than in primary cancers (p 0.01). Trends for more intense staining by grade and decrease in staining in patients administered progressively greater doses of dutastasteride were not statistically significant (p .1).
Conclusions: TMPRSS2 is overexpressed in prostate carcinoma in a stage-associated manner. As a membrane protein, it is a possible target for molecular therapy, as well as a prognostic marker. A question raised by our study is the relationship between overexpression of TMPRSS2 and recent findings that fusion of the TMPRSS2 promoter with a separate gene family - the ets family - is a frequent event in prostate carcinoma. Our finding raises the possibility that TMPRSS2 may be involved in two possibly unrelated molecular events in prostate carcinoma. One allele may by silenced as its promoter is translocated to the ets-located chromosome. The second may be promoted in prostate carcinoma by an independent mechanism.
Category: Genitourinary (including renal tumors)

Tuesday, March 27, 2007 1:15 PM

Platform Session: Section A, Tuesday Afternoon