Lef1 Expression in Androgen-Independent Prostate Cancer
M Zhang, YR Li, LG Wang, J Melamed, XM Liu, JJ Wei, Y Peng, A Pellicer, MJ Garabedian, A Ferrari, P Lee. New York University, New York, NY
Background: A major problem in prostate cancer treatment is the progression of cancer cells to androgen-independent cancer. Markers for this progression are critically needed. Recent evidences suggest aberrant expression of AR (androgen receptor) may play a role in cancer progression and treatment failure. AR expression is potentially regulated by LEF1 in androgen-independent prostate cancer. We examined the expression of LEF1 in androgen-dependent and -independent prostate cancer.
Design: Immunohistochemical study with LEF1 antibody was used to characterize its expression in 99 prostate samples, including 24 cases of benign, 56 cases of androgen-dependent and 19 cases of androgen-independent prostate cancer. Androgen-dependent specimens were derived from patients who were diagnosed with prostate cancer by TURP, having high grade (Gleason 8 or higher) and volume of disease. Androgen-independent samples were derived from patients who underwent TURP at least 6 months after surgical orchiectomy. The immunostaining signal is scored as a combination of intensity (0 as negative, 1+ as weak, 2+ as moderate and 3+ as strong expression) and percentage of positive cells (<10% as 1+ and 10% as 2+) as in any given case with highest score as 5.
Results: Of 24 benign cases, LEF1 is not expressed in luminal cells in all cases and is only expressed in basal cells in certain cases. LEF1 is expressed in 9 of 56 (16%) androgen-dependent cases ranging from 20% to 60% positive cells for a given case. We observed a statistically significant (p<0.01) difference of LEF1 expression between androgen-dependent and -independent cases. LEF1 is expressed in 13 of 19 (66%) androgen-independent cases. The expression of combined score is statistically significantly higher in androgen-independent than -dependent cases (p=0.016).
Conclusions: We demonstrated a dramatic increase of LEF1 expression in androgen-independent disease. The results of this study is consistent with our in vitro data that LEF1 increased AR expression and consequently enhanced growth and invasion ability in androgen-independent cancer cell line. Thus, we identified LEF1 as a potential marker for androgen independent disease.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 123, Wednesday Afternoon