Incidence of KRAS mutations in colorectal carcinomas in a tertiary care centre
Journal Title: Indian Journal of Pathology and Oncology - Year 2017, Vol 4, Issue 4
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second most common cause of adult cancer related deaths worldwide.(1) Carcinoma of the colon and rectum is a relatively uncommon malignancy in India when compared with the western world. Colorectal cancer is generally a disease affecting individuals 50 years of age or older.(2,3,4) It has been estimated that between 2 and 3% of colorectal cancers occur in patients younger than the age of 40 years. Men have proportionately higher incidence of rectal cancer than women.(5,6,7) Colorectal carcinomas (CRCs) evolve through multiple pathways. These pathways may be classified as two different subgroups, which are defined based on their molecular features: (1) chromosomal instability and (2) chromosomal stability. There are hereditary and sporadic tumors in both groups. The minority of hereditary tumors showing chromosomal instability are related to familiar adenomatous polypopsis(FAP) while tumors showing chromosomal stability are hereditary non-polypous colon cancers(HNPCC). Chromosomal instability is characterized by an increased rate of loss or gain of large portions of chromosomes or whole chromosomes. Approximately 85% of sporadic tumors showing chromosomal instability evolve through the classical adenoma-carcinoma sequence. The most frequent mutation in these tumors is the colorectal cancer gatekeeper gene, the APC gene mutation, which involves want signalling mediated by β-catenin.(8) It is always present in FAP patient as a germ line mutation involving one of the alleles. Somatic mutation, loss of heterozygosity (LOH) of the second allele causes the inactivation of the gene. However, APC inactivation is not required in all instances of neoplastic initiation and evolution of colorectal cancers. KRAS and p53 mutations are strongly associated with advanced adenomas. The serrated hyperplastic aberrant crypt foci usually have BRAF mutation, while their minimally serrated counterparts usually have KRAS mutation.(9) KRAS mutation is very strongly associated with a villous architecture(10) and both hyperplastic polyps and serrated adenomas show frequent mutation of the oncogene BRAF as well as extensive DNA methylation, (11) which is much more a feature of tumors showing chromosomal stability. In serrated adenomas without mutation of BRAF, the most frequent mutation is mutation of KRAS. The incidence of K-ras mutation was extremely low in this group of early cancers.(12) According to multistep route of genetic alterations in the colorectal adenoma-carcinoma sequence, KRAS mutation is one of the first alterations to occur.(13) Activating mutations in the KRAS proto-oncogene gene are involved in 25 – 60% of colorectal carcinomas.(14) The importance of KRAS mutation testing for determination of eligibility to receive anti-EGFR therapy has been well established.(15,16)
Authors and Affiliations
Shreya AS
Keywords
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- EP ID EP318142
- DOI 10.18231/2394-6792.2017.0134
- Views 47
- Downloads 0
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