FOXA1 a Poor Prognostic Marker in Prostate Cancer: A Validation Study.
Rohit K Jain, Rutika Mehta, Jae Ro, Harikrishna Nakshatri, Yong Mee Cho, Sunil Badve. Indiana University School of Medicine, Indianapolis; Methodist Hospital, Houston, TX; University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Background: Forkhead box protein A1 (FOXA1), a transcription factor, is important for normal development of the prostate gland. We have previously demonstrated that FOXA1 is marker of poor prognosis that is associated with development of metastasis. The aim of this study was to validate the results of prior exploratory study in a cohort with long term follow up data.
Design: Expression of FOXA1 was analyzed by immunohistochemistry (IHC) in a series of 117 prostate cancers patients selected from the period of 2000 to 2003. Ten tissue microarrays (TMAs) were prepared using 0.6µ triplicate cores from these patients along with one core from corresponding normal tissue adjacent to the tumor foci. All TMAs were stained for FOXA1 using previously described methods and the nuclear expression was noted in primary tumor as well as in normal prostatic tissues using the Histoscore method. Statistical methods used for analyses included Spearman's correlation, Chi-square, and Fisher's exact tests.
Results: High FOXA1 expression in primary prostate tumors correlated positively with positive metastatic status that included cases with nodal and/or distant metastases at surgery or metachronously after surgery (p= 0.010). It also positively correlated with extra-prostatic extension (p = 0.037), seminal vesicle invasion (p=0.048), perineural invasion (p=0.008) and T stage (p= 0.030). It did not correlate with age, PSA level at diagnosis, Gleason score and angiolymphatic invasion.
Conclusions: High FOXA1 expression is related to the development of metastasis. This validation study suggests that FOXA1 expression could be used to identify cancers with a propensity to metastasize fulfilling an unmet need for a predictor of biologic behavior of prostate cancer. In addition, modulating FOXA1expression in prostate cancer may be a potential therapeutic approach.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 159, Monday Afternoon