Solomon James P, Hansel Donna E
Department of Pathology, University of California, San Diego, 200 West Arbor Drive, La Jolla, CA 92103, USA.
Division of Anatomic Pathology, Department of Pathology, University of California, San Diego, 9500 Gilman Drive, MC 0612, La Jolla, CA 92093, USA.
Surg Pathol Clin. 2016 Sep;9(3):391-404. doi: 10.1016/j.path.2016.04.004.
Although there have been many recent discoveries in the molecular alterations associated with urothelial carcinoma, current understanding of this disease lags behind many other malignancies. Historically, a two-pathway model had been applied to distinguish low- and high-grade urothelial carcinoma, although significant overlap and increasing complexity of molecular alterations has been recently described. In many cases, mutations in HRAS and FGFR3 that affect the MAPK and PI3K pathways seem to be associated with noninvasive low-grade papillary tumors, whereas mutations in TP53 and RB that affect the G1-S transition of the cell cycle are associated with high-grade in situ and invasive carcinoma. However, recent large-scale analyses have identified overlap in these pathways relative to morphology, and in addition, many other variants in a wide variety of oncogenes and tumor-suppressor genes have been identified. New technologies including next-generation sequencing have enabled more detailed analysis of urothelial carcinoma, and several groups have proposed molecular classification systems based on these data, although consensus is elusive. This article reviews the current understanding of alterations affecting oncogenes and tumor-suppressor genes associated with urothelial carcinoma, and their application in the context of morphology and classification schema.
尽管最近在与尿路上皮癌相关的分子改变方面有许多发现，但目前对这种疾病的了解仍落后于许多其他恶性肿瘤。从历史上看，一种双途径模型曾被用于区分低级别和高级别尿路上皮癌，尽管最近已描述了分子改变存在显著重叠且日益复杂的情况。在许多病例中，影响MAPK和PI3K途径的HRAS和FGFR3突变似乎与非侵袭性低级别乳头状肿瘤相关，而影响细胞周期G1-S转换的TP53和RB突变则与高级别原位癌和浸润性癌相关。然而，最近的大规模分析已确定这些途径在形态学方面存在重叠，此外，还发现了多种癌基因和肿瘤抑制基因中的许多其他变异。包括新一代测序在内的新技术使对尿路上皮癌的分析更加详细，尽管尚未达成共识，但有几个研究小组已基于这些数据提出了分子分类系统。本文综述了目前对影响与尿路上皮癌相关的癌基因和肿瘤抑制基因的改变的理解，以及它们在形态学和分类模式中的应用。
