PS2 (TFF1) expression in prostate carcinoma: correlation with steroid receptor status

Abstract

pS2 or TFF1 is a member of the trefoil factor family, which is distributed throughout the gastrointestinal tract in both normal and diseased tissues. It is also considered to be one of the major estrogen-regulated proteins and an indicator of estrogen receptor (ER) functionality. pS2 has previously been investigated in benign and malignant prostate lesions with little information about its relationship to steroid receptor status. Our purpose was to correlate pS2 expression with steroid receptor status (ER alpha and progesterone receptor (PR)) and other pathologic variables in prostate carcinoma. 15 benign prostate hyperplasia (BPH) and 47 prostate carcinoma cases were investigated by means of immunohistochemistry for pS2, ER and PR expression. 80% of BPH showed pS2 cytoplasmic immunoreactivity in hyperplastic acini and about half of these cases also exhibited nuclear staining decorating basal or both basal and luminal nuclei. pS2 was highly expressed in prostate carcinoma (91.4%) with both cytoplasmic and nuclear patterns of staining. The latter pattern was significantly associated with carcinoma having a low Gleason score (p=0.02). pS2 lacked any significant correlation with steroid receptor status, stage or grade. Univariate survival analysis revealed a significant impact of stage (p=0.03) and nodal status (p<0.0001) on patient outcome. The diagnostic value of pS2 expression in prostate carcinoma validated 74.19% accuracy, 91.48% sensitivity and 78.18% positive predictive value. The high sensitivity of pS2 expression in prostate carcinoma could make it a suitable marker for diagnosis of prostate carcinoma, especially in metastatic cases of unknown origin. The absence of correlation and dissimilarity in immunolocalization between pS2 and ER alpha leads to the assumption that ER alpha could not be the regulatory protein for pS2 and may raise questions about the functionality of ER alpha in prostate. The nuclear pattern of pS2 immunoreactivity either in benign or malignant prostatic lesions is similar to the published data on ER beta distribution and could also identify a subset of carcinoma patients with a favorable prognosis.