Molecular determinants of tumor recurrence in the urinary bladder

Author:

Cheng Liang1,Zhang Shaobo2,Davidson Darrell D2,MacLennan Gregory T3,Koch Michael O4,Montironi Rodolfo5,Lopez-Beltran Antonio6

Affiliation:

1. Department of Pathology & Laboratory Medicine & Urology, Indiana University School of Medicine, 350 West 11th Street, Clarian Pathology Laboratory Room 4010, Indianapolis, IN 46202, USA.

2. Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, Clarian Pathology Laboratory Room 4010, Indianapolis, IN 46202, USA

3. Department of Pathology, Case Western Reserve University, Cleveland, OH, USA

4. Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

5. Institute of Pathological Anatomy & Histopathology, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy

6. Department of Pathology, Cordoba University, Cordoba, Spain

Abstract

Tumor recurrence is a major clinical concern for patients with urothelial carcinoma of the urinary bladder. Traditional morphological analysis is of limited utility for identifying cases in which recurrence will occur. However, molecular and genetic analyses offer new perspectives on the prediction of bladder tumor recurrence. Recent studies have suggested that urothelial carcinogenesis occurs as a ‘field effect’ that can involve any number of sites in the bladder mucosa. Accumulating evidence supports the notion that resident urothelial stem cells in the affected field are transformed into cancer stem cells by acquiring genetic alterations that lead to tumor formation through clonal expansion. Both initial and recurrent tumors are derived from cancer stem cells in the affected field via two distinct molecular pathways. These provide a genetic framework for understanding urothelial carcinogenesis, tumor recurrence and progression: the FGFR3-associated pathway and the TP53-associated pathway. These two pathways are characterized by different genomic, epigenetic and gene-expression alterations. Their outcomes correlate with the markedly different clinical and pathologic features of both relatively indolent low-grade cancers and the aggressive high-grade cancers. As such, these molecular findings are potentially useful for counseling patients and for assessing risk of recurrence or biological aggressiveness of the patient’s tumor. The molecular changes may additionally prove useful for developing preventive and therapeutic strategies for urothelial bladder cancer. A unifying model of urothelial carcinogenesis, tumor recurrence and progression is proposed in this review.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Oncology,General Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3