Background: To clarify genetic changes in colorectal tumorigenesis, K-ras codon 12 point mutations were examined in 101 ordinary colorectal carcinomas and 6 that complicated ulcerative colitis (UC) with special attention to growth patterns.
Methods: The depths of invasion of ordinary carcinoma were submucosa (SMCa) in 39 cases, muscularis propria (PMCa) in 33, and far-advanced in 29. Growth patterns of SMCa and PMCa were classified into three types: polypoid-growth type without central depression (Type 1), polypoid-growth type with central depression (Type 2), and nonpolypoid-growth type. DNA samples were extracted from formalin fixed paraffin embedded sections, and K-ras codon 12 mutations were examined by two-step polymerase chain reaction-restriction fragment length polymorphism.
Results: K-ras mutation frequency was higher in Type 1 SMCa than in nonpolypoid SMCa, 56% (9/16) versus 6% (1/17), respectively, and in PMCa, 78% (7/9) versus 23% (3/13), respectively. In 6 UC carcinomas, a K-ras mutation was detected in only one polypoid carcinoma and none were detected in five nonpolypoid carcinomas.
Conclusions: These results and the authors' previous study suggest that nonpolypoid carcinomas may be derived from flat adenomas, whose K-ras mutation incidence also was low, and this pathway is different from a genetic model based on the ordinary adenoma-carcinoma sequence through polypoid adenomas.