Polypoid growth and K-ras codon 12 mutation in colorectal cancer.
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.
First Department of Surgery, University of Tokyo, Japan.
S
S
Yamagata
T
T
Muto
Y
Y
Uchida
T
T
Masaki
Y
Y
Higuchi
T
T
Sawada
T
T
Hirooka
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D018256:Adenomatous Polyps / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D001483:Base Sequence; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D017354:Point Mutation
D003062:Codon