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

Clin Genitourin Cancer. 2017 Feb;15(1):e1-e7. doi: 10.1016/j.clgc.2016.06.007. Epub 2016 Jun 27.

Abstract

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.

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

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / metabolism
  • Carbonic Anhydrase IX / metabolism
  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Cycle Proteins / metabolism
  • Diagnosis, Differential
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Variation
  • Humans
  • Kidney Neoplasms / diagnosis*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasms, Multiple Primary / diagnosis*
  • Neoplasms, Multiple Primary / genetics
  • Neoplasms, Multiple Primary / metabolism
  • Neoplasms, Multiple Primary / pathology
  • Neoplasms, Second Primary / diagnosis*
  • Neoplasms, Second Primary / genetics
  • Neoplasms, Second Primary / metabolism
  • Neoplasms, Second Primary / pathology
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Vascular Endothelial Growth Factor A / metabolism
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Cell Cycle Proteins
  • Membrane Proteins
  • PARD3 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Carbonic Anhydrase IX
  • VHL protein, human