Digestive Diseases and Sciences, Vol. 49, No. 6 (June 2004), pp. 954–964 ( C  2004) Prognostic Significance of Mucin Expression in Gastric Carcinoma BELMA KOCER, MD,* ATILLA SORAN, MD,* GULTEN KIYAK, MD,* SIBEL ERDOGAN, MD,† ABDULLAH EROGLU, MD,* BET ¨ UL BOZKURT, MD,* CEM SOLAK, MD,* and OMER CENGIZ, MD* In patients with gastric carcinomas, the role of the alteration of mucin expression in overall survival has been a matter of some speculation, but few studies have been reported. The aim of our study was to determine the relationship between MUC1, MUC2, and MUC5AC expression and patient survival, with a secondary aim designed to investigate the alteration of MUC expression within various clinicopathologic parameters. Forty-four specimens from gastric carcinoma patients were immunohistochemically evaluated using the monoclonal antibodies for MUC1 (EMA, clone E29), MUC2 (CCP58), and MUC5AC (human gastric mucin, clone 45M1). MUC1 expression increased in gastric carcinoma. MUC1 positivity was determined to be statistically significant, with poor clin- icopathological parameters and decreased long-term survival. MUC5AC expression decreased in gastric carcinoma. In addition, patients with MUC5AC-positive tumors also had poor clinicopatho- logical parameters and showed shorter survival than those with MUC5AC-negative tumors. MUC2 expression was not significantly associated with patient survival. We confirmed that the expression of mucins is associated with characteristics of differentiation in gastric carcinoma. Poor patient outcomes were seen in gastric carcinomas with MUC1 mucin expression and MUC5AC positivity. KEY WORDS: gastric carcinoma; mucins; MUC1; MUC2; MUC5AC; prognosis. Mucins constitute the major components of the mucus that protects gastric epithelium from chemical and mechani- cal aggression. It is a high molecular weight glycoprotein consisting of core proteins (apomucin) and O-linked car- bonhydrate side chains. To date, 12 different human mucin genes coding for the apomucins (MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC8, MUC9, MUC11, MUC12) have been identified (1–4). Mucin genes are expressed in a regulated cell- and tissue-specific manner (5, 6). These human mucin genes show cell type-specific expression in the normal stomach. Manuscript received December 10, 2003; accepted March 6, 2004. From the *2nd General Surgery and †Pathology Deparments, Ankara Numune Teaching and Research Hospital, Ankara, 06100, Turkey. This paper was presented at the 12th World Congress of the Inter- national Association of Surgeons and Gastroenterologists, October 30– November 2, 2002, Istanbul, Turkey. Address for reprint requests: Atilla Soran, MD, University of Pitts- burgh, NSABP Center, One Sterling Plaza, 201 N. Craig Street, Pitts- burgh, Pennsylvania 15213, USA; soran@nsabp.pitt.edu. Normal human stomach expresses MUC1, MUC5AC, and MUC6. MUC1 is widely expressed in mucous cells of the surface epithelium of the antrum and is focally expressed in the oxyntic glands of the body and the pyloric glands of the antrum (5–7). MUC5AC is highly expressed in fove- olar cells of the body and the antrum (5, 6, 8), whereas MUC6 is expressed in mucopeptic cells of the neck and in the pyloric glands of the antrum (9, 10). Other mucins are generally absent from the normal gastric mucosa, al- though MUC2 apomucin has been found focally in some stomach samples (11, 12). Alterations of mucin expression take place in gastric carcinomas. It was reported that gastric carcinomas were found to contain a higher level of MUC1 expression than normal gastric mucosa and de novo expression of the MUC2 mucin was observed (6, 13–15). In contrast to the higher expression of MUC1 and MUC2, MUC5AC and MUC6 expression was decreased during gastric carcino- genesis (6, 9, 14, 15). 954 Digestive Diseases and Sciences, Vol. 49, No. 6 (June 2004) 0163-2116/04/0600-0954/0 C  2004 Plenum Publishing Corporation