Ki-ras gene mutations are invariably present in low-grade mucinous tumors of the vermiform appendix

Abstract

Objective. Low-grade mucinous tumors of the appendix appear to have a simple histological structure. Paradoxically, reports have suggested a greater frequency of Ki-ras gene mutation in these lesions than in more complex lesions such as benign colonic adenomas and carcinomas. We assessed several molecular genetic changes, including Ki-ras gene mutations, in a large series of low-grade mucinous tumors of the appendix. Material and methods. We retrospectively ascertained low-grade mucinous tumors of the appendix from computerized pathology records. Extracted DNA was analyzed for APC and DCC gene loss of heterozygosity, microsatellite instability and for the presence of Ki-ras gene mutation using standard molecular techniques. Controls consisted of normal appendices, other appendiceal neoplasms, and ovarian mucinous cystadenomas. Results. A total of 31 low-grade appendiceal mucinous tumors were identified. All were microsatellite stable and none demonstrated loss of heterozygosity for the APC or DCC genes. By contrast, all 31 lesions contained a Ki-ras gene mutation. Conclusions. The presence of a Ki-ras gene mutation in all lesions, with no other molecular changes identified, strongly suggests a possible etiological role of the Ki-ras mutation in the development of this particular lesion of the appendix. Based on other work regarding intestinal bacteria, we hypothesize a relationship between chronic inflammation of the appendix from bacterial overgrowth and Ki-ras gene mutation.

Key Words::

• APC gene loss of heterozygosity
• appendix
• bacterial overgrowth
• DCC gene loss of heterozygosity
• Ki-ras gene mutations
• low-grade mucinous tumors
• microsatellite instability

Acknowledgements

The authors wish to acknowledge the following sources of financial support: H. Nussbaum Foundation of Saint Barnabas Medical Center, Isermann Family Foundation, and Cancer Research, UK.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.