Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers III: Molecular Pathology of Kidney Cancer
Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers III: Molecular Pathology of Kidney Cancer
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DOI：
10.1097/pas.0000000000001476
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发表时间：
2020-07-01
影响因子：
5.6
通讯作者：
Hes, Ondrej
中科院分区：
文献类型：
--
作者：
Williamson, Sean R.;Gill, Anthony J.;Hes, Ondrej
肾细胞癌（RCC）亚型越来越多地通过其分子基础来识别。这通常与组织学和免疫组化替代物相关，因此仅需要简单的靶向分子测定或根本不需要用于诊断确认。在透明细胞RCC中，VHL突变和3 p丢失是众所周知的;然而，其他具有新出现的重要作用的基因包括SETD 2、BAP 1和PBRM 1等。目前已知2型乳头状RCC可能包括几种不同的分子实体，如富马酸水合酶（FH）缺陷型RCC。在MIT家族易位RCC中，现在描述了越来越多的基因融合。一些TFE 3融合伴侣，如NONO、GRIPAP 1、RBMX和RBM 10，由于基因在同一染色体上的接近性，可能显示欺骗性的荧光原位杂交结果。FH和琥珀酸脱氢酶缺陷型肾细胞癌由于遗传性综合征和FH缺陷型肾细胞癌的侵袭性而对患者咨询有影响。免疫组织化学越来越容易获得，有助于识别两者。新出现的肿瘤类型具有明确的诊断实体的有力证据，包括嗜酸性实体和囊性RCC和TFEB/VEGFA/6p 21扩增RCC。其他尚不清楚的新出现的实体包括TCEB 1突变的RCC、伴有ALK重排的RCC、伴有TSC 2或MTOR突变的肾肿瘤和伴有纤维肌间质的RCC。在转移性RCC中，分子研究的作用目前尚未完全确定，尽管与特定治疗途径相关的基因组分析可能发挥越来越大的作用，例如酪氨酸激酶或MTOR抑制剂。
Renal cell carcinoma (RCC) subtypes are increasingly being discerned via their molecular underpinnings. Frequently this can be correlated to histologic and immunohistochemical surrogates, such that only simple targeted molecular assays, or none at all, are needed for diagnostic confirmation. In clear cell RCC, VHL mutation and 3p loss are well known; however, other genes with emerging important roles include SETD2, BAP1, and PBRM1, among others. Papillary RCC type 2 is now known to include likely several different molecular entities, such as fumarate hydratase (FH) deficient RCC. In MIT family translocation RCC, an increasing number of gene fusions are now described. Some TFE3 fusion partners, such as NONO, GRIPAP1, RBMX, and RBM10 may show a deceptive fluorescence in situ hybridization result due to the proximity of the genes on the same chromosome. FH and succinate dehydrogenase deficient RCC have implications for patient counseling due to heritable syndromes and the aggressiveness of FH-deficient RCC. Immunohistochemistry is increasingly available and helpful for recognizing both. Emerging tumor types with strong evidence for distinct diagnostic entities include eosinophilic solid and cystic RCC and TFEB/VEGFA/6p21 amplified RCC. Other emerging entities that are less clearly understood include TCEB1 mutated RCC, RCC with ALK rearrangement, renal neoplasms with mutations of TSC2 or MTOR, and RCC with fibromuscular stroma. In metastatic RCC, the role of molecular studies is not entirely defined at present, although there may be an increasing role for genomic analysis related to specific therapy pathways, such as for tyrosine kinase or MTOR inhibitors.