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Cytokeratin immunophenotype in non-cardia gastric carcinomafrom a population with endemic H. pylori infectionBo Shen, Adrian Ormsby, Chen Shen, John Dumot, Terry Gramlich,Charles Bevins, FACG. The Cleveland Clinic Foundation, Cleveland,OH, and Gastroendoscopy Unit, Qidong City Hospital, Qidong, Jiangsu,China.

Accurate tumor classification is critical for meaningful epidemiologicalstudies in the assessment of cancer incidence and trends. Differentiatingprimary gastric carcinoma from esophageal carcinoma can be difficult,especially when tumors are large and involve both sides of esophagogastricjunction. The histology of tumors from both of these organs is typicallyintestinal type and tumors generally arise in a background of intestinalmetaplasia (IM). Consequently, histologic markers which reliably distin-guish Barrett’s-related esophageal carcinoma from gastric carcinomawould be useful. A unique CK7/CK20 immunophenotype (CK7 �CK20�)was recently described in Barrett’s-related carcinoma (Ormsby AH, et al.Histopathology 2001:38:307–11).Aim: To characterize coordinate CK7 and CK20 expression in the non-cardia gastric adenocarcinoma arising in a background of IM in an endemicpopulation of H. pylori infection and gastric carcinoma.Methods: CK7 and CK20 immunohistochemistry was performed on con-secutive endoscopic biopsy specimens from patients with advanced non-cardia gastric carcinoma. Alcian blue/PAS stains confirmed diagnosis ofIM. H. pylori status was documented with CLO test and/or Giemsa stain.Two GI pathologists, blinded to clinical and endoscopic data, indepen-dently assessed the immunostaining. Immunostaining in �50% of tumorcells of at least moderate intensity was considered positive.Results: Fifty-six patients were enrolled, and 50 patients (89%) had non-cardia gastric carcinoma and background IM. H. pylori infection waspresent in 43 of 50 cases (86%). Forty-nine cases (98%) showed non-Barrett’s carcinoma patterns of CK7/20 staining, ie. CK7�CK20� in 4cases (8%), CK7�CK20� in 33 cases (66%), and CK7�CK20� in 12cases(24%). A CK7�CK20� immunophenotype (Barrett’s-related carcinomapattern) was demonstrated in one case (2%).Conclusion: A CK7�20� tumor immunophenotype, which is associatedwith Barrett’s-related carcinoma, was extremely rare in non-cardia gastriccarcinoma of a population with endemic H. pylori infection.

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Cytokeratin patterns in gastric adenocarcinoma-associated intestinalmetaplasia (IM): further evidence of a distinct disease entityB Shen, AH Ormsby, C Shen, JA Dumot, TL Gramlich, CL Bevins,FACG. The Cleveland Clinic Foundation, Cleveland, OH, andGastroendoscopy Unit, Qidong City Hospital, Qidong, Jiangsu, China.

Background: Esophageal IM (Barrett’s esophagus, BE) and distal gastricIM are morphologically similar and both precede the development ofadenocarcinoma, however, they differ with respect to their clinical presen-tation, epidemiology and pathogenesis. Previously we identified a uniquecytokeratin immunoreactivity pattern (CK7/20) which was strongly asso-ciated with BE. To date, however, this CK pattern has not been evaluatedin gastric IM in patients without risk factors for BE.Aim: To prospectively evaluate CK7/20 patterns in gastric IM associatedwith adenocarcinoma in non-Caucasian patients.Methods: Fifty-six consecutive symptomatic Chinese patients with ad-vanced gastric adenocarcinoma were evaluated. Endoscopic biopsy speci-mens with gastric IM (confirmed with alcian-blue/periodic Schiff stains)adjacent to non-cardia adenocarcinoma were immunostained for CK7 andCK20. Clinical and endoscopic features and H. pylori status were docu-mented. Two blinded gastrointestinal pathologists independently assessedhistology and CK7/20 immunohistochemistry.Results: Fifty of 56 (89%) cases had gastric IM. H. pylori infection, malegender, heartburn/reflux, hiatal hernia �3 cm, and BE were present in 86%,70%, 2%, 0%, and 0% of the cases with gastric IM, respectively. Patchy

CK7 staining was seen in 9 cases (18%) and diffuse CK20 staining in allcases (100%). The Barrett’s CK7/20 pattern characterized by CK7 stainingin superficial and deep glands and CK20 staining in superficial epitheliumwas not seen in any of the 50 cases.Conclusions: The Barrett’s CK7/20 pattern is not present in gastric ade-nocarcinoma-associated IM in a patient population without risk factors forthe development of esophageal adenocarcinoma. Despite the commonpresence of intestinalized mucosa, these results support the hypothesis thatBE and gastric IM associated with adenocarcinoma are two distinct entitieswith unique demographic, clinical, and CK immunophenotypic findings.These results may have application to the evaluation of adenocarcinomasarising at the esophagogastric junction in a background of IM.

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Differential reversal of inhibition of gastric H,K ATPase followingpantoprazole or omeprazole administrationGeorge Sachs* and Jai Moo Shin. 1Medicine, UCLA, Los Angeles, CA,United States.

Purpose: Turnover of the protein of the gastric H,K ATPase without orwith PPI inhibition gives a half-life of �50 hr. Although inhibition byproton pump inhibitors is due to covalent disulfide formation with thegastric acid pump, recovery of acid secretion after cessation of treatment issurprisingly fast in the case of omeprazole and lansoprazole (�24 hr) butslower for pantoprazole (�46 hr). Cysteine #813 is a common binding sitefor all proton pump inhibitors, but cys 822 is uniquely bound by panto-prazole. This cysteine is buried within the transport domain of the pumpand is less accessible to sulfhydryl reagents such as glutathione (GSH).Lack of reversal of binding to this cysteine may account for the longer halflife of pantoprazole inhibition in man.Methods: Rats were treated with either omeprazole or pantoprazole duringhistamine stimulation. The stomach was excised and the ATPase preparedfrom resting or stimulated states by differential and density gradient cen-trifugation. K stimulated ATPase was measured using gastric preparationsfrom untreated and treated rats in the absence and presence of 10 mMdithiothreitol or glutathione for 1 hr. ATPase was quantitated using West-ern blotting with a monoclonal anti-H,K ATPase antibody.Results: The gastric ATPase activity was inhibited by �70% following invivo treatment by either proton pump inhibitor. 10 mM dithiothreitol fullyreversed omeprazole inhibition but did not reverse pantoprazole inhibitionin resting or stimulated membrane fractions. Similar data were obtainedusing glutathione on the stimulated membrane fraction where reversal ofomeprazole but not pantoprazole inhibition was found.Conclusions: Cysteine 813, that is the common binding site for all protonpump inhibitors, is exposed at the luminal surface of the pump based oncrystal structure of the sr Ca ATPase. The additional cysteine, #822 that isbound by pantoprazole, is predicted to be buried in the transport domain ofthe gastric acid pump. Reversal of pump inhibition by omeprazole in vivois probably partly due to GSH dependent removal of the inhibitor atcysteine 813 as well as to turnover of the pump protein. Since GSH cannotremove the inhibitor at cysteine 822, pantoprazole is predicted to have alonger duration of action than other proton pump inhibiors with fulldependence on pump protein turnover.

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Rapid gastric emptying (RGE): is this phenomenon related to age,sex, or early dumping syndrome?Amolak Singh1*. 1Nuclear Medicine, University of Missouri, Columbia,MO, United States.

Purpose: Rapid Gastric Emptying (RGE) is known to occur in patients(pts) with partial gastrectomy or peptic ulcer disease. However, in ourexperience most pts with RGE do not have these conditions. Moreover, therelationship of RGE to age and gender has not been elucidated. The purposeof this study was to determine a) if RGE is related to age or sex, and b) toreview the clinical histories in pts with RGE.

S71AJG – September, Suppl., 2001 Abstracts