Correlation of polypoid colorectal adenocarcinoma with pre-existing adenomatous polyps and KRAS mutation

Cetuximab is an anti–epidermal growth factor receptor that helps effectively treat patients with advanced colorectal adenocarcinoma without KRAS activating mutations. KRAS mutations are associated with 16% to 50% of isolated villous adenomas and approximately 30% of colorectal cancer. Correlation between the gross and histological subset of colorectal adenocarcinoma with KRAS mutation is unknown. Archived surgical resection specimens of colorectal adenocarcinoma (n = 42) and villous adenoma (n = 9) were collected. The gross appearance and histopathological features of these lesions were thoroughly reviewed, including the presence of a pre-existing adenomatous polyp. DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and then subjected to TaqMan real-time polymerase chain reaction to detect the seven most common KRAS mutations. KRAS mutations were found in 13 of 42 cases (31%) of colorectal adenocarcinoma and 7 of 9 cases (78%) of villous adenoma. All 13 cases of colorectal carcinoma with a KRAS mutation showed a gross polypoid configuration, compared to no KRAS mutation in the colorectal carcinomas with ulcerative configuration. In addition, 13 of 17 of these cases (76%) had histological features of adenocarcinoma with a persistent preexisting adenomatous polyp with villous architecture. In summary, grossly polypoid colorectal adenocarcinomas with a persistent pre-existing adenomatous polyp with villous architecture are strongly associated with KRAS mutations.