The genetic alterations of appendiceal carcinomas have not been reported in detail. We studied the clinicopathological factors and genetic alterations including microsatellite instability, p53 overexpression, and mutations of the K-ras proto-oncogene of 30 appendiceal adenocarcinomas, consisting of 23 mucinous and 7 nonmucinous carcinomas. Sixteen (70%) mucinous carcinomas presented with pseudomyxoma peritonei, but 6 of 7 (86%) nonmucinous carcinomas presented with appendicitis (P ‫؍‬ .002). All carcinomas were microsatellite stable, and p53 overexpression was present in only 1 of 30 (3%) carcinomas. K-ras mutation was present in 11 of 20 (55%) carcinomas, including 8 of 16 (50%) mucinous and 3 of 4 (75%) nonmucinous carcinomas. The mean survival of patients with mucinous carcinomas was 26 ؎ 19 months compared with 13 ؎ 9 months for patients with nonmucinous carcinomas (P ‫؍‬ .0002). Our findings suggest that mucinous and nonmucinous carcinomas of appendix have similar genetic alterations, but different clinical presentation and prognosis. KEY WORDS: Adenocarcinoma, Appendix, K-ras, Microsatellite instability, p53. Mod Pathol 2002;15(6):599 -605Appendiceal carcinoma is an uncommon malignancy of the gastrointestinal tract with a prevalence ranging from 0.2 to 0.3% of appendectomy specimens (1, 2). Most appendiceal carcinomas arise from an adenomatous polyp or serrated adenoma (3-5) and present clinically with pseudomyxoma peritonei. Most colorectal cancers develop from adenomatous polyps, and morphological and genetic progression in an adenoma-adenocarcinoma sequence and in hereditary colorectal cancer syndromes are well described (6 -9). The majority of colorectal cancers have truncating mutations or deletions of the adenomatous polyposis coli (APC) gene on chromosome 5q or mutations of the ␤-catenin gene. Point mutations of the K-ras protooncogene and mutations and/or deletions of the p53 gene on chromosome 17p are also common. In a second pathway to colorectal neoplasia, microsatellite instability (MSI; also termed DNA replication errors and ubiquitous somatic mutations) is caused by mutations in a nucleotide mismatch repair gene, including hMSH2, hMLH1, PMS1, PMS2, and GTBP (6 -9). MSI is characterized by additions and deletions of nucleotides in numerous repeated nucleotide sequences (microsatellites). MSI is frequent in the right-sided colon carcinomas and mucinous colorectal carcinomas (6 -9).The genetic alterations in appendiceal carcinoma have not been reported in detail. We therefore studied MSI, p53 overexpression, and K-ras mutations in appendiceal carcinomas and compared these genetic alterations with the clinicopathologic findings. MATERIALS AND METHODS Case MaterialA computer search of MD Anderson Cancer Center surgical pathology diagnoses from 1995 through 2000 was performed. Primary appendiceal carcinomas were identified using the World Health Organization classification of appendiceal carcinomas (10). There were 30 patients with primary appendiceal carcinomas and available paraffin-embedded bloc...