Loss of Heterozygosity at 18q21 and Increased Proliferative Index Are Associated with Appendiceal Mucinous Carcinomatosis
Ki-67 proliferative index >10% was seen in 12/12 AMC and 4/11 LAMN (p=0.001, Fisher's exact). Strong nuclear p53 expression was seen in 3/12 AMC and 0/11 LAMN. Smad4 and p16 expression by IHC showed no correlation with tumor grade, LOH at 18q21 or LOH at 9p21. However, there was abnormal p53 nuclear expression in 4/4 cases with LOH at D17S1289 on 17p13. Interestingly, LOH at 18q21 and 10q23 exclusively occurred in AMC with KRAS mutations. Loss of Smad4 protein expression was also more common in appendiceal neoplasms with KRAS mutations.
Conclusions: In this series, elevated Ki-67 proliferative index, LOH at 18q21 and 10q23 are associated with high tumor grade (AMC). Oncogenic KRAS mutations are frequently found in appendiceal mucinous neoplasms, including localized appendiceal adenomas, indicating that KRAS mutation may be a tumor initiating event. Given that LOH at 18q21 and 10q23 were found exclusively in appendiceal carcinomas with KRAS mutations, LOH at these loci may be associated with genetic progression to carcinoma. Additional studies to evaluate mutations in candidate genes and confirmation of copy number changes involving these chromosomal loci is required.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 83, Wednesday Morning