Analysis of K-ras codon 12 mutations and p53 overexpression in colorectal nodule-aggregating tumors.
OBJECTIVE
Morphologically, colorectal nodule-aggregating tumors are quite different from polypoid-type colorectal tumors that develop via the adenoma-carcinoma sequence. Although polypoid-type colorectal tumors are well known to have a high incidence of K-ras gene mutation and p53 overexpression, colorectal nodule-aggregating tumors have not been examined in terms of genetic changes and clinicopathological features. In the present study, therefore, we analysed the clinicopathological features, genetic changes in K-ras codon 12, and p53 overexpression in colorectal nodule-aggregating tumors.


METHODS
A total of 18 colorectal nodule-aggregating tumors were surgically resected and then analysed clinicopathologically. Immunohistochemistry and polymerase chain reaction-single stranded conformational polymorphism were performed to analyse p53 abnormalities in the tumors. K-ras codon 12 mutations were screened out by the polymerase chain reaction-restriction fragment length polymorphism method and analysed by fluorescence direct sequencing.


RESULTS
p53 overexpression was observed in six lesions (33%). p53-overexpressing cells were observed in parts of carcinoma or adenoma showing high-grade atypia. Four of the 10 (40%) samples had a p53 gene mutation. Nine of the 18 (50%) samples had a K-ras codon 12 point mutation. In eight cases (89%), the mutations of the K-ras codon 12 were of the same type: GGT (glycine) to GTT (valine).


CONCLUSIONS
The colorectal nodule-aggregating tumor has distinctive characteristics showing a morphological phenotype of the superficial-type tumors and genotype of the polypoid tumors in terms of K-ras gene mutation and p53 overexpression.
Kusaka
T
T
Department of Pathology, Dokkyo University School of Medicine, Shimotsuga, Tochigi, Japan.
Fukui
H
H
Sano
Y
Y
Ueda
Y
Y
Chiba
T
T
Fujimori
T
T
D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D018253:Adenoma, Villous / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002432:Cecum / Q000473:pathology; D003062:Codon / Q000235:genetics; D003106:Colon / Q000473:pathology; D012809:Colon, Sigmoid / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012007:Rectum / Q000473:pathology
D003062:Codon; D004273:DNA, Neoplasm