Colorectal cancer (CRC) is one of the most frequent
cancers worldwide.
Adenoma is the main precursor lesion and, recently, the serrated
polyps were described as a group of colorectal lesions with malignant potential. The morphologic and
biologic characterizations of serrated
polyps remain limited. The aim of the present study was to determine the frequency of KRAS and BRAF mutations and
microsatellite instability (MSI) in CRC precursor lesions, to evaluate the association between molecular, pathologic and morphologic alterations in precursor lesions and to compare with the alterations detected in CRC. A series of 342 precursor lesions were removed from 155 patients during colonoscopy. After morphologic classification, molecular analysis was performed in 103 precursor lesions, and their genetic profile compared with 47 sporadic
CRCs.
Adenomas were the main precursor lesions (70.2%). Among the serrated
polyps, the main precursor lesion was hyperplastic
polyps (HPs) (82.4%), followed by sessile serrated
adenomas (12.7%) and traditional serrated
adenomas (2.0%). KRAS mutations were detected in 13.6% of the precursor lesions, namely in
adenomas and in HPs, but in no serrated
adenoma. BRAF mutations were found in 9 (8.7%) precursor lesions, mainly associated with serrated
polyps and absent in
adenomas (P<0.001). High MSI (MSI-H) was absent in precursor lesions. In the 47 CCR cases, 46.8% exhibited KRAS mutation, 6.5% BRAF mutations and 10.6% MSI-H. This study confirms the role of KRAS and BRAF mutations in CRC
carcinogenesis, a crucial step in implementing CRC screening strategies.