Discordance of P53 Mutations of Synchronous Colorectal Carcinomas

Abstract

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.KEY WORDS: P53, Single-strand conformation polymorphism, Synchronous colorectal carcinomas.Mod Pathol 2000;13(2):131-139

Synchronous Colorectal Cancers: A Review of Clinical Features, Diagnosis, Treatment, and Prognosis

“…This gene is considered to be the most prevalent genetic alteration in human neoplasms. Eguchi et al [25] found that in SCRCs, the p53 mutations in left-sided and rectal carcinomas were different from those in right-sided carcinomas (p = 0.04), supporting the idea that SCRCs may be of multicentric origin [26]. In addition, Yalcinkaya et al [27] showed that p53 expression in SCRCs was strongly associated with aggressiveness and poor prognosis; specifically, adenocarcinomas with poor differentiation and deeper invasion had higher expression of p53.…”

Complete single-stage management of left colon cancer obstruction with a new device

“…Although these big polyps were not malignant, if they had been found postoperatively as with conventional IACI method, another laparotomy might have been performed because of the size and risk of perforation in the case of endoscopic removal. The incidence of two or more primary colorectal carcinomas has been estimated to range between 2% and 11% of all carcinomas in the colon and rectum [1,6,9,11,18,27].…”

Synchronous Trifocal Colorectal Cancer

“…Nonetheless, the most current estimates of incidence are still considered to be inaccurate since not all tumors are discovered clinically and the number of related population studies is still relatively low. Genetic and molecular pathways associated with colorectal cancer synchronicity, such as microsatellite instability, altered expression of p53, and gene promoter methylation have received increasing attention in the pertinent literature (15)(16)(17)(18)(19)(20). In addition, distinct clinical features of patients with multiple colorectal lesions (such as age, male gender, metastasis rates) have been studied, yet their prognostic signifi cance remains inconclusive.…”