Identical clonal origin of synchronous and metachronous low-grade, noninvasive papillary transitional cell carcinomas of the urinary tract
Identical clonal origin of synchronous and metachronous low-grade, noninvasive papillary transitional cell carcinomas of the urinary tract
复制标题
DOI：
10.1016/s0046-8177(99)90037-0
复制
发表时间：
1999-10-01
期刊：
影响因子：
3.3
通讯作者：
Cannizzaro, LA
中科院分区：
文献类型：
--
作者：
Li, MM;Cannizzaro, LA
尿路乳头状移行细胞癌(PTCC)最重要的生物学特征之一是其多中心性和复发倾向。已经提出了两种可能的机制，场效应和粘膜内播种/扩散。前者假设致癌物引起多个尿路上皮细胞的同步或异时性恶性转化(独立克隆起源)，后者推测同步和异时性肿瘤起源于肿瘤细胞的植入或直接扩散(相同的克隆起源)。我们通过分析位于X染色体的雄激素受体基因(HUMARA)的甲基化模式来验证这些假说。我们使用福尔马林固定的石蜡包埋组织成功地分析了35例异时性和同步性的、低级别(1级或2级)、非侵入性的来自10名杂合子女性患者的尿路pTCC。其中复发性膀胱癌4例，复发性膀胱癌16例，异时性膀胱癌和输尿管肾盂肿瘤各4例，多发灶肿瘤2例，均为单克隆性肿瘤。此外，在任何给定患者的多个复发或多灶性肿瘤中检测到相同的甲基化等位基因，表明它们具有相同的克隆来源。我们得出结论，低级别、非侵袭性的pTCC本质上是单克隆性的。同时性或异时性的pTCC具有相同的克隆起源，有力地支持了粘膜内播种/扩散假说。版权所有(C)1999，由W.B.Saunders公司提供。
One of the most important biological features of papillary transitional cell carcinoma (pTCC) of the urinary tract is its multicentricity and its tendency for recurrences. Two possible mechanisms, field effect and intramucosal seeding/spreading, have been proposed. The former theory hypothesizes that carcinogenic agents cause synchronous or metachronous malignant transformation of multiple urothelial cells (independent clonal origin), and the latter speculates that synchronous and metachronous tumors are derived from implantation or direct spreading of tumor cells (identical clonal origin). We tested these hypotheses by analyzing the methylation patterns of the androgen receptor gene (HUMARA) located at the X-chromosome, Thirty-five metachronous and synchronous, low-grade (grade 1 or 2), noninvasive pTCCs of the urinary tract from 10 heterozygous female patients were successfully analyzed using formalin-fixed, paraffin-embedded tissue. These included 16 recurrent bladder tumors from 4 patients, 10 metachronous bladder and ureter/renal pelvis tumors from 4 patients, and 9 multifocal tumors from 2 patients, All tumors are monoclonal as indicated by unbalanced methylation of HUMARA. Furthermore, same methylated allele was detected in multiple recurrent or multifocal tumors from any given patient, indicating their identical clonal origin. We conclude that low-grade, noninvasive pTCCs are monoclonal in nature. Synchronous or metachronous pTCCs have an identical clonal origin, strongly supporting the intramucosal seeding/spreading hypothesis. Copyright (C) 1999 by W.B. Saunders Company.