Characteristics of Advanced- and Non Advanced Sporadic Polypoid Colorectal Adenomas: Correlation to KRAS Mutations

The malignant potential of colorectal adenomas highly correlates with their pathological characteristics, such as size, histology and grade of dysplasia. Currently, based on these parameters, adenomas are characterized as “non-advanced or advanced” and patient surveillance is adjusted accordingly. The aim of this study was to investigate the correlation between the KRAS mutations and characteristics of non-advanced and advanced colorectal adenomas for predicting the risk of increased malignant potential of adenomas that may influence the decision to offer follow-up endoscopic surveillance. We used a mutagenic polymerase chain reaction – restriction fragment length polymorphism method to determine KRAS mutations in 164 colorectal sporadic polypoid adenomas (51 non-advanced-, 113 advanced adenomas) and in 40 early colorectal carcinomas. The method of mutation detection was validated according to recommendation for KRAS mutation testing in colorectal carcinoma of the European Quality Assurance Program. The limit of detection of the assay was 3 % mutated DNA with a good reproducibility. Evaluation of pathological characteristics was performed according to European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis. The morphological parameters of the adenoma such as size, histology, grade of dysplasia are highly correlated with one another: an increasing adenoma size raised the proportion of villous histology and degree of dysplasia (all p < 0.0001). KRAS mutations were detected in 31 % of the non-advanced adenomas, in 57.5 % of the advanced adenomas and in 62.5 % of the early carcinomas. Most mutations occurred at codon 12 rather than at codon 13 (72 %, 82 %, 76 % versus 22 %, 17 %, 24 %, respectively). There was no significant difference in association of KRAS mutation with age, gender, location among non-advanced-, and advanced adenomas and early carcinomas. KRAS mutation was found more often in tubulovillous and villous adenomas, whereas wild-type KRAS was observed more frequently in tubular adenomas (P < 0.0001) and there was an increased prevalence of KRAS mutations in larger adenomas (P < 0.0001). In this study KRAS mutation occurred with the same frequency in adenomas with low-grade (48 %) and high-grade (50 %) dysplasia. KRAS mutation is very strongly associated with a villous architecture and through villous component expansion, KRAS mutations may increase risk of tumor progression in sporadic colorectal polypoid adenomas.