were histologically assessed according to the updated Sydney-classification, in 845 patients (mean age 55y) with H. pylori infection and no peptic ulcer or gross pathology were identified and further analyzed according to gastritis phenotypes, Prevalence of corpus-predominant gastritis (CPG), intestinal metaplasia (IM) and severe atrophy (SATR) were evaluated. Results: The age-adjusted prevalence of the gastritis phenotype was independent of the gender. Prevalence of histological characteristics considered for risk assessment are shown in the table. Conclusion: The prevalence of gastritis features at risk for cancer developmem increases with age. Among the investigated gastritis phenotypes 1M at any location as well as the combination of IM+CPG showed the highest increase being 4-fold for IM as well as for combinod CPG with IM at the age of 65 years versus less than 45 years These findings reinforce the necessity for the histological assessment even in subjects with a normal endo- scopic appearance The age-dependent increase in prevalence n[ risk gastritis phenotypes however does not allow to estimate the individual risk for gastric cancer development - only the follow-up vail tell us. 845 114 120 15t 199 166 95 CPG(%) 154 68 125 119 151 229 200 IN(%) 241 79 117 185 251 392 400 ,~ATR (%) 109 88 67 7.3 151 127 126 CPG~IM (%) 64 0,9 l II 33 20 ......... 6, 5 127 126 W1328 Identification of Osteopontin as a serum marker of ampullary carcinoma by gene expression profiling Tjarda Van Heek, Anirban Maitra, Jens Koopmann, Neff Fedarko, Alka Jain, Ayman Rahruan, Christine Iacobuzio-Donahue, Volkan Adsay, Raheela Ashlaq, Charles Yet, John L Cameron, Johan A. Offerhaus, Ralph Hruban, Karin D Berg, Michael Goggins Background: ,Gmpullary adenocarcinoma is an aggressive cancer with a poor prognosis. The area of this study was to use olignnucleotide microarrays to identify differentially expressed gettes in ampullary adenocarcinoma to better understand the biology of this disease and to identify potential markers for the early diagnosis of ampullary cancer. Materials & Methods: The Altymetrix Human Genome U133 GeneChip set (HG-U133A and HG-U133B) was used to obtain gene ex-pression profiles of 5 ampullary cancer and 10 normal duodenal samples. The Afiymetrix Data Mining Tool software was utilized to assess the genes that were overex- pressed in ampullary carcinoma compared to normal duodenum. Results: Over 500 genes were identified as 3-tbld or greater e.xpressed in ampunary cancers compared to normal duodenum. The expression profiles of nine candidate overexpressed genes (osteopontin, PSCA, mesothetin, T1MP-1, mucin-1, mucin-5, fascin, heat shock protein 47, fibronectin 1) were confirmed by immunohistocbemistry or in situ hybridization on tissue micro arrays (TMA) containing 54 ampullan/ cancers. One of the genes ovarexpressed on the tissue micoarrays was osteopontin, which was expressed > 20-fold higher in ampullary adenocarci- noruas compared to normal duodenum by genechip analysis We therefore detelmined sernm osteopontin levels in ampuliary neoplasms and normal controls. Mean pre-operative serum osteopomin levels as measured by competitive ELtSA were 906 ng/ml (range 268 ng/ml) in patients with ampullary cancer, 867 ng/ml (range 160 ng/ml) in patients with an ampunary adenoma, and 204 ng/ml (range 65 ng/ml) in sera from age-matcbed healthy controls (P<0.O01). Using a cut-off of 2 standard deviations above the mean, sera from patients with ampullary neoplasms could be distinguished from healthy controls with a sensitivity of 100% and specificity of 95%. Conclusion: These results demonstrate that elevated serum osteopontin is a sensitive marker of ampullary adenoearcinoma and highlight the utility of gene expression profiling to identify" candidate tumor markers. W1329 Piru-10ncogene: a Novel Biomarker of Gastrointestinal Primary and Metastatic Adenocareinomas Simona Di Cart, Swaminathan Rajendiran~ Rajiv Dhir, EmilLa Carloni, Antonio Gasbarrini, Antonia Sepulveda Backgruund: Gastrointestinal (GI) carcinomas represent the second most common malignan- cies in the US, Pim-1 is a serine-threonine protein kinase. We recently identified pim-1 as a novel gene that is expressed in gastric carcinoma cells and found that it is induced by H. pylori, a known tnalor risk factor in gastric cancer development, Atins: To evaluate pim-1 as a diagnostic tool to assess the site of origin of GI adenocarcinomas and specifically to distinguish upper (,gastric and esophageal) from distal GI carcinomas (colorectal), based on evaluation of pim-1 expression in metastatic as well as in primary lesions. Methods: The expression of Pim-1 was evaluated in 64 adenocarcinomas (15 esophageal, 23 gastric and 26 colorectal) and non-neoplastic adjacent mucosa. L)anph node metastases were examined in five cases Fire-l was detected by mamunohistochemical stains of tbrmalin-fixed paraffin embedded tissue sections with a polycloual anti-pim-1 goat antibody (Santa Cruz). Three difterent scores were given depending on the percentage of positive tumor cells (Score 0: Pim-1 expression in <5% tumor cells; Score I: >5% <30% tumor cells; Score 2: >30% tumor cells). Resuhs: Plm-1 (score 2) was expressed in esophageal (9/15; 60%) and stomach (19/23; 82.6%) but not in colorectal adenocarcinomas (0/26) (p<0.0001). Normal gastric and colonic mucosa expressed low levels of piru-l, Of five cases of metastatic carcinoma in lymph nodes, the pim-1 immunoreactivity in the primary tumor was similar to the pattern in the metastatic loci. Conclusions: in this study we show that the pim-1 protooncogene is differentially expressed in stomach and esophageal carcinomas as compared to colorectal adenecarcinomas, making pim-1 an excellent biomarker to help identify" the site of origin of these tumors. Together, these fndings indicate that pim-1 is a novel biomarker for the differemial diagnosis of upper gastrointestinal adenocareinomas (esophageal and gastric) and lower gastrointestinal carcinomas (from the colorectum). W1330 The Correlation Between Lymph Node Metastasis and The Depth of Submueosal Invasion in Submueosal Colorectal Carcinoma in Japan-A Report from The Japanese Society for Cancer of The Colon and Rectuuru Kazuaki Kitajima, Jun Takeda, Shigehiko Fujii, Ko NagasakG Shingo Ishiguro, Tadakatzu Shiruoda, Akinori lwashita, Yo Kato, Yoichi Aiioka, Hidenobu Watanabe, Tetsuichirn Mutt, Takahiro Fujimori Background/Aim: It has been reported that [,vmph nodes metastasis occurs in only 83-i2% of patients with submucosal colorectal carcinoma. Most submucosal colorectal carcinoma without 1Dnph nodes metastasis would be considered suitable for endoscopic treatment. However, clear indications tor endoscopic treatment of submucosal colorectal carcinoma have not been establish. The Japanese Society for Cancer of the Colon and Rectmn has been attempting to determine the criteria tbr grading submucosaI colorectal carcinomas on the basis of the depth of submucosal invasion in order to clarify the indications for endoscopic treatment of submucosal colorectal carcinoma The aim of this study is to clarify the character- istic of submucosal colorectal carcinoma with lymph uode metastasis by using the criteria of the Japanese Society for Cancer of the Colon and Rectum. Methods: Eight hundred seventy seven submucosal colorectal carcinomas that have been resected surgically at 6 flcilines were analyzed. All cases were classified by the status of mnscularis mucosae on H.E stein into 3 types: type A- muscularis mucosae could be recognized clearly; type B- muscularis mucosae could not be recognized clearly but could be assumed; type C- mnscularis ruucosae could not be assumed. In type A and B, the depth of submucosal invasion was measured flora the Iower edge of muscularis mucosae or assumed muscularis mucosae to the deepest tnvasivr portion, in type C, it was measured from superficial of tmnor, but in the case o~ pedunculated type by macroscopic classification, it was measured from the level 2 line in Haggitt's classification. The case whose submucosal deepest invasive portion was limited to the upper level 2 was defined as head invasion. Results: Lymph node metastasis were observed in 92 of 877 submucosal colorectal carcinomas (I 0.4%), and they were not observed in cases with depth of invasion less than 1000 ~xm and head invasion. The rate of lymph nodes metastasis classified according to the depth of submucosaI invasion was as f01Iows: 11.0% (17/155) in 1000-2000 Ixm, 13559% (24/177) in 2000-3000 t~m, 13.563% (51/ 376) in over 3000 lain. Conclusion: These results suggest that submucosaI colorectal carcino- mas with depth of invasion less than 1000 ixm and head invasion have no lymph node metastasis and these cases would be become indications for endoscopic treatment. W1331 Nueleosomal DNA hypermethylation detected in sera of colon cancer patients as a marker of cancer surveillance Mikihiro Fujiya, Toshifumu Ashida, Kotaro Okamoto, Jun Sakamoto, Yubei Inaba, Yasuko Miyoshi, Atsuo Maemoto, Fnmika Orii, Atsumi Yasuda, Jim watan, Tokiyoshi Ayabe, Yusnke Saito, Yutaka Kohgo Background/Aim: For cancer screening, detection of tumor-specific DNA alteratioits in the sera has been considered to be highly specific, but the clinical application has been suspended because of the limitation of the sensitivity, and the heterogenity of the targeted mutation sites/types of the gene. DNA hypermethylation of cancer suppressor gene promotor, such as p16 promoter, is relatively common alteration observed in various cancers. However, the sensitivity of the detection of p16 hypermethylation in serum DNA has bee reported only 23-30% in colon cancer patieuts. To increase the sensitivity of the assay, we developed the novel method by collecting the nucleosonre DNA from the serum sample, whmh contains the de-acetylated histones tightly combined to methylated DNA sequences. Materials~lethods: Primary colorectal cancer tissues and serum samples were collected from 51 patients operated in our hospital. Comrol serum samples were obtained from 4 patients with adenomatons polyps and 10 healthy volunteers. Serum DNA samples were prepared by DNA absorbing- resin. Nucleosome DNA in sera was prepared by immunoprecipitation with anti-histone H1 monoclonal antibody followed by DNA extraction, p16 promoter hypermethylation (p16 HM) in both DNA preparations were analyzed by methylation specific PCR (MSP). DNA samples isolated from colorectal tissues were also subjected to MSP. Results: p16 HM was detected in 26/51 tissue samples. In these 26 patients, p16 HM was detected in 22/26 (85%) by nudeosome DNA preparation, In contrast, only 16/26 (62%) of conventional serum DNA preparation showed p16 HM. Especially, in stage I1 colorectal cancers, sensitivity of MSP with necleosome DNA ( 11/15; 73 %) is signifcamly higher than that with conventional serum DNA preparation (6115; 43%). No false-positive result was obtained from control DNA samples. Conclusions: Nucleosome DNA preparation from the serum sample increased the sensitMty for detecting p16 HM rather than the conventional serum DNA preparation in colon cancer patients, especially in stage II patients with curable diseases. The overall sensitivity of the single gene analysis is still remained limited, however, combination of other hypermethylated genes to the targets of the nucleosome DNA analysis warrant the possible application for colon cancer surveillance. W1332 The Fate of Indefinite Dysplasia in Ulcerative Colitis Nimj Jani, Asher Kornbluth, Victoria Croog, Noam Harpaz, Steven ltzkowitz, Thomas U]lman Background: Little is known about the time-dependent risk of neoplastic progression in ulcerative colitis (UC) patients (pts) with mueosal changes interpreted as indefinite for dysplasia (IND). Aim: To determine whether 1ND found at surveillance colonoscopy has a different rate of neoplastic progression than if no dysplasia is found. Methods: From the G[ Pathology database, we identified all pts who underwent surveillance colonoscopy for UC in 1996-7 and reviewed their medical records. We identified a cohort of pts with IND found at surveillance without prior history of neoplasia (fiat low-grade dysplasia (LGD), high-grade dysplasia (HGD), or cancer (CRC)). A comparable cohort with no dysp[asia (NOD) consisted of pts with a negative surveillance exam within two months of an IND subject, and with a similar number of previous negative exams. Cohorts were analyzed by lit~-table methods A-649 AGA Abstracts