Discordance of p53 mutations of synchronous colorectal carcinomas.
It is unclear whether synchronous multiple tumors arise from multicentric or monoclonal origins. To verify the multicentric origin of synchronous colorectal carcinomas at a genetic level, immunohistochemical and molecular techniques were used to determine the p53 alterations in individual lesions of synchronous colorectal carcinomas. This study was based on a total of 32 colorectal tumors from 16 patients. Twenty-one of the 32 (66%) advanced tumors examined had positive staining for p53. Single-strand conformation polymorphism and polymerase chain reaction direct sequencing were carried out for exons 5 to 8 of p53. All cases had p53 mutations in one or more tumors of synchronous lesions. In nine patients in this series, individual lesions were found to carry a different mutated codon of the p53 gene. In the other seven patients, a p53 mutation was found in one tumor but not in another. These results indicate discordance of the mutation pattern of p53 in individual lesions of multiple colorectal carcinomas and support the idea that most synchronous colorectal carcinomas are genetically distinguishable and are multicentric in origin. We also confirmed the high frequency of p53 mutations in left-sided (71%) and rectal (91%) carcinomas, rather than right-sided (43%; P = .04) carcinomas, suggesting that the molecular mechanism of synchronous colorectal carcinomas might differ between right- and left-sided tumors in the same patient.
Eguchi
K
K
Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yao
T
T
Konomoto
T
T
Hayashi
K
K
Fujishima
M
M
Tsuneyoshi
M
M
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D017431:Genes, MCC; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D017931:DNA Primers; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53