Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 1;48(3):329-336.
doi: 10.1097/PAS.0000000000002176. Epub 2024 Jan 19.

Prognostic Value of BAP1 Protein Expression in Uveal Melanoma

Susan Kennedy  1   2 , Sally Owens  1   2 , Laura Ivers  2 , Ciara Hegarty  1   2 , Valerie O'Neill  1 , Jose J Berenguer-Pina  3 , Noel Horgan  4 , John Crown  2   3 , Naomi Walsh  2
Affiliations

Prognostic Value of BAP1 Protein Expression in Uveal Melanoma

Susan Kennedy et al. Am J Surg Pathol. .

Abstract

The prognostic value of the traditional pathologic parameters that form part of the American Joint Committee on Cancer staging system and genetic classifications using monosomy chromosome 3 and structural alterations in chromosome 8 are well established and are part of the diagnostic workup of uveal melanoma (UM). However, it has not been fully clarified whether nuclear protein expression of the tumor suppressor gene BAP1 (nBAP1) by immunohistochemistry alone is as powerful a predictor of overall survival (OS) and/or disease-specific survival (DSS) as chromosome analysis. The protein expression of nBAP1 was evaluated in a retrospective cohort study of 308 consecutive patients treated by primary enucleation between January 1974 and December 2022. We correlated clinical, pathologic, and cytogenetic characteristics to identify the best prognostic indicators for OS and DSS. Loss of nBAP1 was detected in 144/308 (47%) of patients. Loss of nBAP1 expression was significantly associated with poor survival. In patients with disomy chromosome 3, nBAP1 negative is significantly associated with poorer OS but not DSS. We observed that older age (>63 years), presence of metastasis, and nBAP1 negative remained independent prognostic factors in multivariate analysis. nBAP1 protein expression proved to be a more reliable prognostic indicator for OS than the American Joint Committee on Cancer staging, M3 status, or The Cancer Genome Atlas classification in this cohort. This study provides support for accurate prognostication of UM patients in routine histology laboratories by immunohistochemistry for nBAP1 alone.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Figures

FIGURE 1
FIGURE 1
Kaplan-Meier OS and DSS curves stratified by (A and B) nBAP1-positive and nBAP1-negative expression and (C and D) nBAP1-positive, nBAP1-negative, and cBAP1-positive (nBAP1 negative) expression by IHC. Log-rank tests were used to compare OS and DSS across groups. DSS indicates disease-specific survival; OS, overall survival.
FIGURE 2
FIGURE 2
Impact of nBAP1 expression based on chromosome 3 status. Kaplan-Meier curves in patients stratified based on chromosome 3 monosomy (A) OS (B) DSS, and Kaplan-Meier curves in patients stratified based on chromosomal 3 disomy (C) OS and (D) DSS and nBAP1 expression. DSS indicates disease-specific survival; OS, overall survival.
FIGURE 3
FIGURE 3
Forest plot of the univariate Cox regression analysis for overall survival (A) and disease-specific survival (B) in all patients.
See this image and copyright information in PMC

References

    1. Robertson AG, Shih J, Yau C, et al. . Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell. 2017;32:204–220. - PMC - PubMed
    1. Mahendraraj K, Lau CS, Lee I, et al. . Trends in incidence, survival, and management of uveal melanoma: a population-based study of 7,516 patients from the Surveillance, Epidemiology, and End Results database (1973-2012). Clin Ophthalmol. 2016;10:2113–2119. - PMC - PubMed
    1. Rantala ES, Hernberg M, Kivelä TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res. 2019;29:561. - PMC - PubMed
    1. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118:1881–1885. - PubMed
    1. Nathan P, Hassel JC, Rutkowski P, et al. . Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021;385:1196–1206. - PubMed