Towards the Development of a Multiplex Prostate Cancer Specific Biomarker.
Kyung Park, Samprit Banerjee, Francesca Demichelis, Mark A Rubin. Weill Cornell Medical College, New York
Background: Trefoil factor 3 (TFF3), polypeptides secreted by normal human intestinal mucosa, is associated with various cancers and found to be over-expressed in a subset of prostate cancers. Previous work suggests that the common TMPRSS2-ERG fusion can down-regulate TFF3 expression in hormone-naïve prostate cancer. Given this inverse expression relationship, we wanted to test if a combined marker could serve as a prostate cancer specific biomarker.
Design: Double staining with immunohistochemistry (IHC) produced protein expression data of nuclear ERG and cytoplasmic TFF3 on a tissue microarray composed of cases with known mRNA expression data generated by Next Generation RNA sequencing (RNA-Seq).
Results: 41% of the cases had positive nuclear staining for ERG and 71 % had positive cytoplasmic staining for TFF3 with more than 50% of the cells. Out of 63 cases, 13 had both ERG and TFF3 staining in the same cancer cells with inversely correlated intensities (p=0.00827, Generalized Fisher test). The relationship between ERG and TFF3 expression was confirmed by ERG gene rearrangement status with FISH (p=2.6e-05, Fisher's test). Out of 34 tumors without ERG gene rearrangement, 22 had moderate or strong TFF3 expression. 21 out of 23 ERG rearranged tumors had no or weak TFF3 expression. It was 18 times more likely to have high TFF3 protein expression in tumors without ERG rearrangement. 7% of the cases had neither ERG gene rearrangement (4/57) nor ERG/TFF3 protein expression (5/63). When the protein expression was compared to mRNA transcript level, there was a linear correlation for both ERG (p=0.004) and TFF3 (p=3.8e-06). 6 tumor cases had matching benign tissues: 3 had weak and focal (less than 10% of the cells) positivity with TFF3 IHC.
Conclusions: This study demonstrates that the protein expression of ERG and TFF3 corresponds to the mRNA expression. 92% of tumors had over-expression of either ERG or TFF3 so the feasibility of combining ERG and TFF3 as biomarker for primary prostate cancer should be further explored.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 8:30 AM
Platform Session: Section A, Monday Morning