Synchronous Metastatic Clear-Cell Renal Cell Carcinoma: A Distinct Morphologic, Immunohistochemical, and Molecular Phenotype

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• 作者：Solene-Florence Kammerer-Jacquet¹ ; ² ; ^{jacquet.sf@gmail.com} ; Angelique Brunot³ ; Adelaide Pladys⁴ ; Guillaume Bouzille⁵ ; Julien Dagher¹ ; Sarah Medane² ; Benoit Peyronnet⁶ ; Romain Mathieu⁶ ; Gregory Verhoest⁶ ; Karim Bensalah⁶ ; Julien Edeline³ ; Brigitte Laguerre³ ; Alexandra Lespagnol⁷ ; Jean Mosser⁷ ; Frederic Dugay⁸ ; Marc-Antoine Belaud-Rotureau² ; ⁸ ; Nathalie Rioux-Leclercq¹ ; ²
• 关键词：Clear cell renal cell carcinoma ; Clinical outcome ; Sarcomatoid component ; Synchronous and metachronous metastases ; VEGF ; VHL gene
• 刊名：Clinical Genitourinary Cancer
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：15
• 期：1
• 页码：e1-e7
• 全文大小：881 K
• 卷排序：15

文摘

Clear cell renal cell carcinomas (ccRCCs) are highly metastatic tumors with metastases detected at diagnosis (synchronous) or during follow-up (metachronous). To date, there have been no reports comparing primary ccRCC of patients with synchronous and metachronous metastases, who are different in terms of prognosis. Determining whether there is a phenotypic difference between these 2 groups could have important clinical implications.Patients and MethodsIn a retrospective consecutive cohort of 98 patients with ccRCC, 48 patients had metastases, including 28 synchronous and 20 metachronous presentations, with a follow-up of 10 years. For each primary tumor in these metastatic patients, pathologic criteria, expression of vascular endothelial growth factor, partitioning-defective 3, CAIX, and programmed death ligand 1 as detected by immunohistochemistry, and complete VHL status were analyzed. Univariate analysis was performed, and survival was assessed using Kaplan-Meier curves compared by log-rank test.ResultsCompared with primary ccRCC in patients with metachronous metastases, primary ccRCC in patients with synchronous metastases were significantly associated with a poorer Eastern Cooperative Oncology Group performance (P = .045), higher pT status (P = .038), non-inactivated VHL gene (P = .01), sarcomatoid component (P = .007), expression of partitioning-defective 3 (P = .007), and overexpressions of vascular endothelial growth factor (> 50%) (P = .017) and programmed death ligand 1 (P = .019). Patients with synchronous metastases had a worse cancer-specific survival than patients with metachronous metastases even from metastatic diagnosis (median survival, 16 months vs. 46 months, respectively; P = .01).ConclusionThis long-term study is the first to support the notion that synchronous m-ccRCC has a distinct phenotype. This is probably linked to the occurrence of oncogenic events that could explain the worse prognosis. These particular patients with metastases could benefit from specific therapy.