Eguchi K, Yao T, Konomoto T, Hayashi K, Fujishima M, Tsuneyoshi M
Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mod Pathol. 2000 Feb;13(2):131-9. doi: 10.1038/modpathol.3880024.
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.
同步性多发肿瘤是起源于多中心还是单克隆尚不清楚。为了在基因水平验证同步性结直肠癌的多中心起源，采用免疫组化和分子技术来确定同步性结直肠癌各个病灶中的p53改变。本研究基于16例患者的32个结直肠肿瘤。在32个接受检查的进展期肿瘤中，有21个（66%）p53染色呈阳性。对p53基因的第5至8外显子进行了单链构象多态性分析和聚合酶链反应直接测序。所有病例在同步性病灶的一个或多个肿瘤中都存在p53突变。在本系列的9例患者中，发现各个病灶携带不同的p53基因突变密码子。在其他7例患者中，在一个肿瘤中发现了p53突变，而在另一个肿瘤中未发现。这些结果表明，多个结直肠癌各个病灶中p53的突变模式不一致，并支持这样一种观点，即大多数同步性结直肠癌在基因上是可区分的，且起源于多中心。我们还证实，左侧（71%）和直肠（91%）癌中p53突变的频率较高，而非右侧（43%；P = .04）癌，这表明同一患者左右侧同步性结直肠癌的分子机制可能不同。
