Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low-risk clear cell renal cell carcinoma

Authors

  • Richard W. Joseph MD,

    Corresponding author
    1. Division of Medical Oncology, Mayo Clinic Florida, Jacksonville, Florida
    • Corresponding author: Richard W. Joseph, MD, Assistant Professor, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Fax: (904) 953-8508; joseph.richard@mayo.edu

    Search for more papers by this author
    • The first 2 authors contributed equally to the manuscript.

  • Payal Kapur MD,

    1. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
    Search for more papers by this author
    • The first 2 authors contributed equally to the manuscript.

  • Daniel J. Serie BS,

    1. Departments of Health Sciences Research and Medicine, Mayo Clinic Florida, Jacksonville, Florida
    Search for more papers by this author
  • Jeanette E. Eckel-Passow Ph. D,

    1. Department of Health Sciences Research, Mayo Clinic Rochester, Rochester, Minnesota
    Search for more papers by this author
  • Mansi Parasramka Ph.D,

    1. Division of Cancer Biology, Mayo Clinic Florida, Jacksonville, Florida
    Search for more papers by this author
  • Thai Ho MD, Ph.D,

    1. Division of Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, Arizona
    Search for more papers by this author
  • John C. Cheville MD,

    1. Division of Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, Arizona
    Search for more papers by this author
  • Eugene Frenkel MD,

    1. Division of Hematology-Oncology, Department of Internal Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas
    Search for more papers by this author
  • Dinesh Rakheja MD,

    1. Department of Pathology and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
    Search for more papers by this author
  • James Brugarolas MD, Ph.D,

    1. Division of Hematology-Oncology, Department of Internal Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas
    2. Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas
    Search for more papers by this author
    • The last 2 authors are co-senior authors.

  • Alexander Parker PhD

    1. Departments of Health Sciences Research and Medicine, Mayo Clinic Florida, Jacksonville, Florida
    Search for more papers by this author
    • The last 2 authors are co-senior authors.

Errata

This article is corrected by:

  1. Errata: Erratum: Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low-risk clear cell renal cell carcinoma Volume 120, Issue 11, 1752–1753, Article first published online: 22 February 2014

Abstract

BACKGROUND

The majority of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have low-risk disease with a < 10% chance of ccRCC-specific death. DNA sequencing revealed that mutations in BAP1 (BRCA1 associated protein-1) occur in 5% to 15% of ccRCC cases and are associated with poor outcomes. The vast majority of BAP1 mutations abolish protein expression. In this study, we used a highly sensitive and specific immunohistochemistry (IHC) assay to test whether BAP1 expression is an independent marker of ccRCC-specific survival, particularly in patients with low-risk disease.

METHODS

BAP1 expression was assessed, using IHC, in 1479 patients who underwent nephrectomy to treat clinically localized ccRCC. A centralized pathologist dichotomized patients as either BAP1-positive or BAP1-negative. The authors employed Kaplan-Meier and Cox regression models to associate BAP1 expression with cancer-specific survival.

RESULTS

A total of 10.5% of tumors were BAP1-negative, 84.8% of tumors were BAP1-positive, and 4.6% of tumors had ambiguous staining for BAP1. Patients with BAP1-negative tumors have an increased risk of ccRCC-related death (hazard ratio [HR] = 3.06; 95% confidence interval [CI] = 2.28-4.10; P = 6.77 × 10−14). BAP1 expression remained an independent marker of prognosis after adjusting for the UCLA integrated staging system (UISS) (HR = 1.67; 95% CI = 1.24-2.25; P < .001). Finally, BAP1 was an independent prognostic marker in low-risk patients with a Mayo Clinic stage, size, grade, and necrosis (SSIGN) score of ≤ 3 (HR = 3.24; 95% CI = 1.26-8.33; P = .015).

CONCLUSIONS

This study used a large patient cohort to demonstrate that BAP1 expression is an independent marker of prognosis in patients with low-risk (SSIGN≤ 3) ccRCC. Cancer 2014;1059–1067. © 2014 American Cancer Society.

Ancillary