Association and Significance of Myc, Estrogen Receptor, and Metastasis-Associated Gene 1 (MTA1) Expression in Advanced Prostate Cancer
MD Hofer, D Pflueger, S Perner, R Kim, F Demichelis, R Kuefer, MA Rubin. Brigham and Women's Hospital, Boston, MA; Weill Cornell Medical College, New York, NY; University of Ulm, Ulm, Germany
Background: Overexpression of Myc and MTA1 is observed in many cancers. Myc is amplified in advanced prostate cancer (PCa) but there is no association between amplification and expression. Recent reports describe that Myc expression may be regulated by estrogen receptor (ER) and that MTA1 is a downstream effector of Myc. In the current study we analyzed protein expression of ER, Myc, and MTA1 in 114 clinically localized and advanced PCa cases to determine their association with each other and its significance for PCa progression.
Design: ER, Myc and MTA1 expression levels were evaluated on a scale of 1-4 by immunohistochemistry (IHC) on TMAs. We also determined ERG rearrangement for a subset of cases with FISH to identify its effect on this pathway.
Results: Mean patient age was 65 yrs (48-77), mean pre-operative PSA level 29.3 ng/ml (1-248), max follow-up time 154 months (mean 31.4). PSA recurrence occurred in 42/114 patients (37%), 21/114 (18%) were stage pT2 and 83/114 pT3 (82%), 77/114 (68%) were pN+ and 37/114 (32%) pN0. Gleason scores of 4-6 was found in 15/114 (13%) patients, score of 7 in 35/114 (31%), score of 8-10 in 64/114 (56%). Myc and MTA1 expression were significantly elevated in lymph node metastases compared to primary PCa (p<0.000 each, Chi-Square test), no difference was seen for ER. Expression levels of ER, Myc, and MTA1 were significantly associated with each other (ER-Myc (r=0.35, p<0.000), Myc-MTA1 (r=0.411, p<0.000), ER-MTA1 (r=0.263, p=0.008). Myc expression was also associated with Gleason score (R=0.209, p=0.028). Cox regression analysis revealed both Myc and MTA1 expression to be predictors of PSA recurrence (Myc: HR 1.51 (1.04-2.19), p=0.032; MTA1: HR 1.39 (1.02-1.89), p=0.036). No difference in Myc and MTA1 expression depending on ERG rearrangement was observed, but high Myc expression was a greater risk factor for PSA recurrence in ERG rearranged PCa (HR: 2.65 (1.1-6.4), p=0.031).
Conclusions: The association between ER, Myc and MTA1 expression suggest that these proteins are components of one progression pathway in prostate cancer. Myc and MTA1 expression are significantly associated with PSA recurrence and development of lymph node metastases and this appears to be accentuated in ERG rearranged cancers. We are currently expanding our analysis to functional assays in cell culture.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 95, Wednesday Morning