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

Solène-Florence Kammerer-Jacquet (1, 2) , Angélique Brunot (3) , Adélaide Pladys (4) , Guillaume Bouzille (5, 6) , Julien Dagher (2, 7) , Sarah Médane (8) , Benoit Peyronnet (9) , Romain Mathieu (9) , Grégory Verhoest (9) , Karim Bensalah (9, 6) , Julien Edeline (10, 11, 12) , Brigitte Laguerre (11) , Alexandra Lespagnol (8) , Jean Mosser (2, 8) , Frédéric Dugay (2, 7) , Marc-Antoine Belaud-Rotureau (2, 7) , Nathalie Rioux-Leclercq (2, 8)

1 Service de Pathologie [Rennes] = Pathology [Rennes]
2 IGDR - Institut de Génétique et Développement de Rennes
3 CRLCC - CRLCC Eugène Marquis
4 EHESP - École des Hautes Études en Santé Publique [EHESP]
5 CIC - Centre d'Investigation Clinique [Rennes]
6 LTSI - Laboratoire Traitement du Signal et de l'Image
7 Service de Cytogénétique et de Biologie Cellulaire
8 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
9 Service d'urologie [Rennes] = Urology [Rennes]
10 Foie, métabolismes et cancer
11 Département d'oncologie médicale [Rennes]
12 NuMeCan - Nutrition, Métabolismes et Cancer

INTRODUCTION: 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 METHODS: In 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.RESULTS: Compared 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).CONCLUSION: This 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.

Mots clés: VHL gene; Sarcomatoid component; Clinical outcome; Synchronous and metachronous metastases; Clear cell renal cell carcinoma; VEGF

Domaines: Cancer; Urologie et Néphrologie

Solène-Florence Kammerer-Jacquet, Angélique Brunot, Adélaide Pladys, Guillaume Bouzille, Julien Dagher, et al.. Synchronous Metastatic Clear-Cell Renal Cell Carcinoma: A Distinct Morphologic, Immunohistochemical, and Molecular Phenotype. Clinical Genitourinary Cancer, 2017, 15 (1), pp.e1-e7. ⟨10.1016/j.clgc.2016.06.007⟩. ⟨hal-01470708⟩