Trefoil factor 3 overexpression in prostatic carcinoma: Prognostic importance using tissue microarrays

BACKGROUND. Human intestinal trefoil factor 3 (TFF3) is a member of a family of polypeptides encoded by a cluster of genes on chromosome 21. Through gene expression profiling studies TFF3 mRNA has been found to be overexpressed in prostate cancer. METHODS. We used immunochemistry on tissue microarrays and software tools, collectively referred to as TMAJ, for online assessment of staining to analyze samples from 294 primary tumors and 61 metastatic lesions. RESULTS. Applying a cutoff of 20% of cells staining as positive, the frequency of staining was 18.8% in normal (51 of 272) and 47.0% in primary tumors (126 of 268), P < 0.0001, Wilcoxon rank sum). Expression of TFF3 in metastatic prostate cancer was similar to that in primary tumors. TFF3 expression was not associated with time to biochemical recurrence, development of distant metastasis, or death due to prostate cancer. Scoring data derived from visual estimation of expression correlated highly with semi-automated image analysis using the Automated Cellular Imaging System (ACIS™) from Chromavision, Inc. CONCLUSIONS. These studies validate that TFF3 is overexpressed at the protein level in a subset of primary and metastatic prostate cancers, show the first use of the TMAJ database, and demonstrate the ability to semi-automatically scan and score immunohistochemically stained tissue microarray slides.