Crupi Emanuele, Costa de Padua Tiago, Marandino Laura, Fallara Giuseppe, Pederzoli Filippo, Cimadamore Alessia, Goetz Emanuele C, Cigliola Antonio, Patané Damiano A, Mercinelli Chiara, Tateo Valentina, Salonia Andrea, Briganti Alberto, Montorsi Francesco, Meeks Joshua J, Spiess Philippe E, Alhalabi Omar, Gao Jianjun, Kamat Ashish M, Grivas Petros, Necchi Andrea, Raggi Daniele
Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
JCO Precis Oncol. 2024 Dec;8:e2400470. doi: 10.1200/PO-24-00470. Epub 2024 Dec 3.
Aberrant expression of nectin-4 (N4) has been observed in several malignancies emerging as new target for antibody-drug conjugates, especially in urothelial carcinoma of the bladder (UBC). Limited data on N4 positivity in nonurothelial genitourinary (GU) cancers are available. This systematic-review aimed to investigate N4 positivity among GU malignancies.
A systematic literature review was performed on March 2023 using PubMed, MEDLINE, and Embase databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Protocol was amended to incorporate a new updated search on March 2024.
Twenty-five studies evaluating N4 positivity in GU tumors were included, 14 on UBC, three on upper tract urothelial carcinoma (UTUC), six on histologic subtypes (HS) and divergent histology of the bladder, one on papillary renal cell carcinoma (pRCC), one in chromophobe RCC (chRCC), two on penile cancer, one in prostate cancer (PCa). Among UBC, stratifying per stage N4 positivity was higher in metastatic (weighted mean [WM], 90.8; range, 59.6-100) and in non-muscle-invasive (WM, 87.4; range, 86.7-88.3) than in muscle-invasive UC (WM, 83.1; range, 68.2-100). The N4 positivity of UBC was higher than UTUC (WM, 62.9; range, 44.4-65.7). Immunohistochemistry N4 positivity was reported to be lower in non-UC malignancies, including pRCC (WM, 44.1; range, 44.1-44.1), HS (WM, 63.5; range, 0-100), PCa (WM0; range, 0-0), chRCC (WM, 18.5; range, 18.5-18.5), and penile cancer (WM, 86.5; range, 61.4-98.3), compared with UBC overall (WM, 87.1; range, 59.6-100).
Non-UC malignancies seem to have a lower N4 positivity rate than UC. N4 positivity in bladder cancer appears to vary according to stage and presence of HS. The predictive and prognostic role of N4 must be further characterized in larger and prospective studies.
已在多种恶性肿瘤中观察到NECTIN-4（N4）的异常表达，其作为抗体药物偶联物的新靶点而出现，尤其是在膀胱尿路上皮癌（UBC）中。关于非尿路上皮泌尿生殖系统（GU）癌症中N4阳性的数据有限。本系统评价旨在调查GU恶性肿瘤中的N4阳性情况。
根据系统评价和Meta分析的首选报告项目声明，于2023年3月使用PubMed、MEDLINE和Embase数据库进行了系统文献综述。2024年3月对方案进行了修订，纳入了新的更新搜索。
纳入了25项评估GU肿瘤中N4阳性的研究，其中14项关于UBC，3项关于上尿路尿路上皮癌（UTUC），6项关于膀胱的组织学亚型（HS）和不同组织学类型，1项关于乳头状肾细胞癌（pRCC），1项关于嫌色性肾细胞癌（chRCC），2项关于阴茎癌，1项关于前列腺癌（PCa）。在UBC中，按分期分层，N4阳性在转移性（加权均值[WM]，90.8；范围，59.6 - 100）和非肌层浸润性（WM，87.4；范围，86.7 - 88.3）中高于肌层浸润性UC（WM，83.1；范围，68.2 - 100）。UBC的N4阳性高于UTUC（WM，62.9；范围，44.4 - 65.7）。据报道，在包括pRCC（WM，44.1；范围，44.1 - 44.1）、HS（WM，63.5；范围，0 - 100）、PCa（WM0；范围，0 - 0）、chRCC（WM，18.5；范围，18.5 - 18.5）和阴茎癌（WM，86.5；范围，61.4 - 98.3）在内的非UC恶性肿瘤中，免疫组织化学N4阳性低于总体UBC（WM，87.1；范围，59.6 - 100）。
非UC恶性肿瘤的N4阳性率似乎低于UC。膀胱癌中的N4阳性似乎因分期和HS的存在而有所不同。N4的预测和预后作用必须在更大规模的前瞻性研究中进一步明确。
