非转移性透明细胞肾细胞癌肾实质浸润或小结节扩散的预后影响和基因组背景。

IF 7.1 1区 医学 Q1 PATHOLOGY
Hajime Tanaka , Yuki Fukawa , Kouhei Yamamoto , Kousuke Tanimoto , Akira Takemoto , Takayasu Mori , Hisashi Hasumi , Mayumi Kinoshita , Takumi Kanazawa , Asuka Furukawa , Koichiro Kimura , Hiroyuki Sato , Akihiro Hirakawa , Shohei Fukuda , Yuma Waseda , Soichiro Yoshida , Steven C. Campbell , Yasuhisa Fujii
{"title":"非转移性透明细胞肾细胞癌肾实质浸润或小结节扩散的预后影响和基因组背景。","authors":"Hajime Tanaka ,&nbsp;Yuki Fukawa ,&nbsp;Kouhei Yamamoto ,&nbsp;Kousuke Tanimoto ,&nbsp;Akira Takemoto ,&nbsp;Takayasu Mori ,&nbsp;Hisashi Hasumi ,&nbsp;Mayumi Kinoshita ,&nbsp;Takumi Kanazawa ,&nbsp;Asuka Furukawa ,&nbsp;Koichiro Kimura ,&nbsp;Hiroyuki Sato ,&nbsp;Akihiro Hirakawa ,&nbsp;Shohei Fukuda ,&nbsp;Yuma Waseda ,&nbsp;Soichiro Yoshida ,&nbsp;Steven C. Campbell ,&nbsp;Yasuhisa Fujii","doi":"10.1016/j.modpat.2024.100590","DOIUrl":null,"url":null,"abstract":"<div><p>A subset of clear cell renal cell carcinomas (ccRCCs) exhibits various growth patterns that infiltrate the normal renal parenchyma; however, our understanding of its association with cancer aggressiveness is incomplete. Here, we show that the morphology of the tumor interface with normal renal parenchyma is robustly associated with cancer recurrence after surgery, even when compared with the TNM staging system or the World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grade in nonmetastatic ccRCC. Hematoxylin and eosin–stained slides of whole tissue sections from surgical specimens were analyzed using a cohort of 331 patients with nonmetastatic ccRCC treated with radical nephrectomy. The patients were classified into 10 subgroups based on our classification algorithms for assessing the tumor interface with normal renal parenchyma. Among the 10 subgroups, 4 subgroups consisting of 40 patients (12%) were identified to have aggressive forms of nonmetastatic ccRCC associated with poor prognosis and unified as renal parenchymal infiltration or micronodular spread (RPI/MNS) phenotypes. Multivariable analyses showed that RPI/MNS phenotypes were robustly associated with shorter disease-free survival, independently of existing pathological factors including the TNM staging system and WHO/ISUP nuclear grade. The hazard ratio was highest for RPI/MNS (4.62), followed by WHO/ISUP grades 3 to 4 (2.11) and ≥pT3a stage (2.05). In addition, we conducted genomic analyses using next-generation sequencing of infiltrative lesions in 18 patients with RPI/MNS and tumor lesions in 33 patients without RPI/MNS. Results showed that alterations in <em>SETD2</em> and <em>TSC1</em> might be associated with RPI/MNS phenotypes, whereas alterations in <em>PBRM1</em> might be associated with non-RPI/MNS phenotypes. These data suggest that RPI/MNS may be associated with aggressive genomic backgrounds of ccRCC, although more comprehensive analyses with a larger sample size are required. Future studies may further elucidate the clinical implications of RPI/MNS, particularly for deciding the indication of adjuvant treatment after nephrectomy.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 11","pages":"Article 100590"},"PeriodicalIF":7.1000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prognostic Impact and Genomic Backgrounds of Renal Parenchymal Infiltration or Micronodular Spread in Nonmetastatic Clear Cell Renal Cell Carcinoma\",\"authors\":\"Hajime Tanaka ,&nbsp;Yuki Fukawa ,&nbsp;Kouhei Yamamoto ,&nbsp;Kousuke Tanimoto ,&nbsp;Akira Takemoto ,&nbsp;Takayasu Mori ,&nbsp;Hisashi Hasumi ,&nbsp;Mayumi Kinoshita ,&nbsp;Takumi Kanazawa ,&nbsp;Asuka Furukawa ,&nbsp;Koichiro Kimura ,&nbsp;Hiroyuki Sato ,&nbsp;Akihiro Hirakawa ,&nbsp;Shohei Fukuda ,&nbsp;Yuma Waseda ,&nbsp;Soichiro Yoshida ,&nbsp;Steven C. Campbell ,&nbsp;Yasuhisa Fujii\",\"doi\":\"10.1016/j.modpat.2024.100590\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>A subset of clear cell renal cell carcinomas (ccRCCs) exhibits various growth patterns that infiltrate the normal renal parenchyma; however, our understanding of its association with cancer aggressiveness is incomplete. Here, we show that the morphology of the tumor interface with normal renal parenchyma is robustly associated with cancer recurrence after surgery, even when compared with the TNM staging system or the World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grade in nonmetastatic ccRCC. Hematoxylin and eosin–stained slides of whole tissue sections from surgical specimens were analyzed using a cohort of 331 patients with nonmetastatic ccRCC treated with radical nephrectomy. The patients were classified into 10 subgroups based on our classification algorithms for assessing the tumor interface with normal renal parenchyma. Among the 10 subgroups, 4 subgroups consisting of 40 patients (12%) were identified to have aggressive forms of nonmetastatic ccRCC associated with poor prognosis and unified as renal parenchymal infiltration or micronodular spread (RPI/MNS) phenotypes. Multivariable analyses showed that RPI/MNS phenotypes were robustly associated with shorter disease-free survival, independently of existing pathological factors including the TNM staging system and WHO/ISUP nuclear grade. The hazard ratio was highest for RPI/MNS (4.62), followed by WHO/ISUP grades 3 to 4 (2.11) and ≥pT3a stage (2.05). In addition, we conducted genomic analyses using next-generation sequencing of infiltrative lesions in 18 patients with RPI/MNS and tumor lesions in 33 patients without RPI/MNS. Results showed that alterations in <em>SETD2</em> and <em>TSC1</em> might be associated with RPI/MNS phenotypes, whereas alterations in <em>PBRM1</em> might be associated with non-RPI/MNS phenotypes. These data suggest that RPI/MNS may be associated with aggressive genomic backgrounds of ccRCC, although more comprehensive analyses with a larger sample size are required. Future studies may further elucidate the clinical implications of RPI/MNS, particularly for deciding the indication of adjuvant treatment after nephrectomy.</p></div>\",\"PeriodicalId\":18706,\"journal\":{\"name\":\"Modern Pathology\",\"volume\":\"37 11\",\"pages\":\"Article 100590\"},\"PeriodicalIF\":7.1000,\"publicationDate\":\"2024-08-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Modern Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0893395224001704\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Modern Pathology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0893395224001704","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

透明细胞肾细胞癌(ccRCC)的一个亚群表现出各种浸润正常肾实质的生长模式;然而,我们对其与癌症侵袭性的关联性的了解并不全面。在这里,我们发现肿瘤与正常肾实质的交界形态与术后癌症复发密切相关,即使与 TNM 分期系统或世界卫生组织/国际泌尿病理学会(WHO/ISUP)对非转移性 ccRCC 的核分级进行比较也是如此。我们对 331 名接受根治性肾切除术的非转移性 ccRCC 患者的手术标本全组织切片进行了血色素和伊红染色切片分析。根据我们评估肿瘤与正常肾实质界面的分类算法,将患者分为 10 个亚组。在这10个亚组中,有4个亚组的40名患者(12%)被确定为具有侵袭性的非转移性ccRCC,预后较差,并被统一为肾实质浸润或微结节扩散(RPI/MNS)表型。多变量分析表明,RPI/MNS表型与较短的无病生存期密切相关,不受TNM分期系统和WHO/ISUP核分级等现有病理因素的影响。RPI/MNS的危险比最高(4.62),其次是WHO/ISUP 3-4级(2.11)和≥pT3a期(2.05)。此外,我们还利用新一代测序技术对18例RPI/MNS患者的浸润性病灶和33例无RPI/MNS患者的肿瘤病灶进行了基因组分析。结果显示,SETD2和TSC1的改变可能与RPI/MNS表型有关,而PBRM1的改变可能与非RPI/MNS表型有关。这些数据表明,RPI/MNS 可能与 ccRCC 的侵袭性基因组背景有关,但还需要进行样本量更大的更全面的分析。未来的研究可能会进一步阐明 RPI/MNS 的临床意义,尤其是在决定肾切除术后辅助治疗的适应症方面。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prognostic Impact and Genomic Backgrounds of Renal Parenchymal Infiltration or Micronodular Spread in Nonmetastatic Clear Cell Renal Cell Carcinoma

A subset of clear cell renal cell carcinomas (ccRCCs) exhibits various growth patterns that infiltrate the normal renal parenchyma; however, our understanding of its association with cancer aggressiveness is incomplete. Here, we show that the morphology of the tumor interface with normal renal parenchyma is robustly associated with cancer recurrence after surgery, even when compared with the TNM staging system or the World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grade in nonmetastatic ccRCC. Hematoxylin and eosin–stained slides of whole tissue sections from surgical specimens were analyzed using a cohort of 331 patients with nonmetastatic ccRCC treated with radical nephrectomy. The patients were classified into 10 subgroups based on our classification algorithms for assessing the tumor interface with normal renal parenchyma. Among the 10 subgroups, 4 subgroups consisting of 40 patients (12%) were identified to have aggressive forms of nonmetastatic ccRCC associated with poor prognosis and unified as renal parenchymal infiltration or micronodular spread (RPI/MNS) phenotypes. Multivariable analyses showed that RPI/MNS phenotypes were robustly associated with shorter disease-free survival, independently of existing pathological factors including the TNM staging system and WHO/ISUP nuclear grade. The hazard ratio was highest for RPI/MNS (4.62), followed by WHO/ISUP grades 3 to 4 (2.11) and ≥pT3a stage (2.05). In addition, we conducted genomic analyses using next-generation sequencing of infiltrative lesions in 18 patients with RPI/MNS and tumor lesions in 33 patients without RPI/MNS. Results showed that alterations in SETD2 and TSC1 might be associated with RPI/MNS phenotypes, whereas alterations in PBRM1 might be associated with non-RPI/MNS phenotypes. These data suggest that RPI/MNS may be associated with aggressive genomic backgrounds of ccRCC, although more comprehensive analyses with a larger sample size are required. Future studies may further elucidate the clinical implications of RPI/MNS, particularly for deciding the indication of adjuvant treatment after nephrectomy.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信