Polypoid growth and K‐ras codon 12 mutation in coiorectal cancer

Abstract

Background. To clarify genetic changes in coiorectal tumorigenesis, K‐ras codon 12 point mutations were examined in 101 ordinary coiorectal 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. Cancer 1995;75:953‐7. Copyright © 1995 American Cancer Society