FOXA1 Expression Predicts Likelihood of Metastasis in Prostate Cancer
RK Jain, R Mehta, MT Idrees, H Nakshatri, S Badve. Indiana University, Indianapolis, IN
Background: The clinical course of prostate cancer is difficult to predict with most cancer patients dying with cancer rather than of cancer. None of the currently available predictive markers can a priori identify tumors that will give rise to metastases. For the development of personalized therapy of cancer patients, markers that accurately and reliably predict outcome are required. FOXA1, a transcription factor, is important for normal development of the prostate gland. Its expression is thought to be controlled by steroid hormones and GATA-3, another transcription factor. The aim of this study is to understand the expression and potential role of FOXA1 and GATA3 transcription factors as prognostic factors in prostate cancer.
Design: Expression of FOXA1 and GATA-3 in addition to androgen, estrogen and progesterone receptors was retrospectively analyzed by IHC in a series of 80 primary tumors and 28 metastatic prostate cancers selected from the period of 2003 to 2009. All sections were stained for FOXA1, GATA-3, AR, ER and PR using previously described methods and the nuclear expression was noted in primary and metastatic tumor tissues as well as in normal prostatic tissues adjacent to the tumor area using Histoscore method. Statistical methods used included Spearman's correlation, Chi-square, Fisher's exact and Mann-Whitney tests.
Results: Expression of AR did not significantly differ in primary and metastatic tumors. Strong FOXA1 expression was seen in 30% of primary tumors and 89% of metastatic tumors (p<0.0001). FOXA1 expression correlated positively with AR, N stage, cancer dimension, and extra-prostatic extension but did not correlate with age, PSA level at diagnosis, T stage, Gleason score, presence of PIN or multifocality, seminal vesicle or perineural invasion. A trend for positive correlation was observed with angiolymphatic invasion. Expression of ER, PR or GATA-3 was not seen in either normal epithelium or tumor.
Conclusions: FOXA1 appears to play a significant role in the patho-physiology of the development of metastatic prostate cancer. If this preliminary data is confirmed, FOXA1 expression could be used to identify cancers with a propensity to metastasize. In addition, modulating FOXA1 expression in prostate cancer may be a potential therapeutic approach.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 125, Monday Morning