Pergamon EumpeonJoumalojCancVol. 32A, No. 9, pp. 1585-1590, 1996 Copyright 0 1996 Elsevier Science Ltd. All rights reserved Printed in Great Britain 0959-8049196 515.OOiO.00 PII: SO959-8049(96)00116-S Original Paper pS2 Protein Expression in Gastric Carcinoma. An Immunohistochemical and Immunoradiometric Study zyxwvutsrqponm J.-C. Machado,’ F. Carneiro,’ P. Ribeiro,2 N. Blin’ and M. Sobrinho-Simdes’ ‘Department of Pathology, IPATIMUP, Medical Faculty, Universityof Porro, H.S. Joso, 4200 Pox-to, Portugal; 2Department of Clinical Pharmacology,Portuguese Instituteof Oncology, Porto, Portugal; and ‘Instirut fiir Authropologieund Humangenerlk, UniversitPt Tubingen, Tubingen, Germany The aim of this study was to examine the prevalence of pS2 expression in gastric carcinoma and to determine its prognostic significance. We analysed pS2 protein expression in 50 gastric carcinomas and respective adjacent mucosas by immunohistochemistry and immunoradiometric assay (IRMA). pS2 was consistently expressed in superficial and foveolar epithelium of non-neoplastic mucosa and in 66.0% of the carcinomas. pS2 immunoreactivity was significantly higher in diffuse than in intestinal carcinomas, and in those cases with nodal metastases than in those without. No correlation was found between pS2 immunostaining and gender, age, staging, depth of wali penetration, venous invasion, ploidy and S-phase tiaction. The mean levels of pS2 (IRMA) were significantly lower in gastric carcinomas than in n.on-neoplastic mucosas, and were not correlated with any of the aforementioned clinicopathological features. The survival of patients with pS2-positive tumours was not significantly different from that of patients with pS2-negative tumours. We conclude that pS2 expression, which can be used as a marker of gastric-type differentiation, is associated with gastric carcinoma of diffuse type. The lack of correlation between pS2 expression and most features of tumour aggressiveness and patients’ survival precludes its use as ,a prognostic tool in gastric carcinoma. Copyright 0 1996 Elsevier Science Ltd Key words: gastric carcinoma, immunohistochemistry, immunoradiometric assay (II&VIA), mucins, pS2, stomach, survival, trefoil peptides zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA EurJCancer, Vol. 32A, NO. 9, pp. 158%1590,1996 INTRODUCTION pS2 PROTEIN is a member of the trefoil peptide family whose gene was cloned from the MCF-7 breast cancer cell line by Masiakowski and colleagues [ 11. In human breast cancer, pS2 is associated, though not exclusively, with oestrogen receptor expression [2-41, responsiveness to hormone therapy [5] and favourable prognosis [6, 71. In normal human tissues, and excluding the pS2 expression in some apparently normal breast specimens [4, 81, pS2 has only been consistently detected in the superficial and foveolar epithelium of gastric mucosa [9-141. The few published reports on pS2 immunoexpression in gastric carcinoma [lo, 14-161 provide discrepant data on some of the clinicopathological parameters under analysis. Theisinger and colleagues [16] observed pS2 expression of Correspondence to J.-C. Machado. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Revised 3 Feb. 1996; accepted 8 Feb. 1996. variable intensity in every carcinoma of their series, whereas the prevalence of pS2 immunoreactivity varied from 48 to 57 per cent in other series [ 10, 14, 151. In contrast to Miiller and Borchard [ 141 who did not find any significant relationship between pS2 expression and the histological type, Theisinger and colleagues [ 161 found a close association between diffuse gastric carcinoma and a high percentage of strongly stained pS2 immunoreactive cells. Finally, Miiller and Borchard [14] reported a significant relationship between pS2 expression and extent of tumour growth (pT stage); despite this, they did not observe any significant influence of the immunohisto- chemical expression of pS2 on the outcome of the patients zyxwvuts P41. We undertook the present immunohistochemical and immunoradiometric study of pS2 in a series of gastric carci- nomas in an attempt to settle the aforementioned discrep- ancies. We also intended to determine whether the immuno- histochemical evaluation of pS2 carries any meaningful 1585