Goto K, Konomoto T, Hayashi K, Kinukawa N, Naito S, Kumazawa J, Tsuneyoshi M
Second Department of Pathology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Mod Pathol. 1997 May;10(5):428-37.
The purpose of this study is to assess whether the development of synchronous and/or metachronous multifocal urothelial cancers is due to field defect, intraluminal seeding and implantation, or both. We used a series of 42 cases of multiple urothelial cancers. We performed polymerase chain reaction single-strand conformation polymorphism, DNA sequencing, and immunohistochemical studies on p53 gene mutations in 84 multiple urothelial carcinomas (78 urinary bladder carcinomas and 6 ureteric or renal pelvic carcinomas) from 42 patients. p53 Mutations were detected in 42 (50%) of 84 cancerous tumors from 22 (52%) of the 42 patients and were strongly related to the tumor grade but not to the tumor stage. Nine patients had identical mutations with or without additional mutations in the multiple carcinomas, which suggests that the carcinomas had a common origin. Eleven patients, however, had discordant mutations, and two patients had a mutation in one tumor but not in another, a fact that strongly suggests independent origin. Double mutations were observed in 9 (21%) of 42 patients; in these types of mutation, transitions were clearly more frequent than transversions, a difference from previously reported spectra of urothelial carcinomas. The data indicate that multiple urothelial carcinomas seem to be either common or of independent origin. In addition, the different p53 mutational spectra in this series might reflect the presence of other possible mutagens in carcinogenesis of multiple urothelial carcinomas.
本研究的目的是评估同步和/或异时性多灶性尿路上皮癌的发生是由于场缺陷、腔内播散和种植，还是两者皆有。我们使用了一系列42例多发性尿路上皮癌病例。我们对42例患者的84例多发性尿路上皮癌（78例膀胱癌和6例输尿管或肾盂癌）进行了聚合酶链反应单链构象多态性分析、DNA测序以及p53基因突变的免疫组化研究。在42例患者中的22例（52%）的84个癌性肿瘤中有42个（50%）检测到p53突变，且与肿瘤分级密切相关，但与肿瘤分期无关。9例患者在多发性癌中存在相同突变，伴有或不伴有其他突变，这表明这些癌具有共同起源。然而，11例患者存在不一致的突变，2例患者在一个肿瘤中有突变而在另一个肿瘤中没有，这一事实强烈提示为独立起源。在42例患者中有9例（21%）观察到双重突变；在这些类型的突变中，转换明显比颠换更频繁，这与先前报道的尿路上皮癌谱不同。数据表明，多发性尿路上皮癌似乎要么具有共同起源，要么为独立起源。此外，本系列中不同的p53突变谱可能反映了多发性尿路上皮癌致癌过程中存在其他可能的诱变剂。
