Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression

• Type of Material: Article
• Authors: Gustav Stalhammar, St. Erik Eye Hospital, Stockholm; Hans Grossniklaus, Emory University
• Language: English
• Date: 2021-03-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cancers13051143
• Title of Journal or Parent Work: CANCERS
• Volume: 13
• Issue: 5
• Start Page: 1
• End Page: 15
• Grant/Funding Information: Carmen and Bertil Regnér Foundation (reference 2020-00062); Region Stockholm (reference 20200356); Karolinska Institutet (reference 2019-01900, 2020-013333 and 2020-02517); The Royal Swedish Academy of Sciences (reference ME2019-0036); Support for this study was provided to Gustav Stålhammar from:; The Crown Princess Margareta Foundation for the Visually Impaired (reference 157); The Swedish Society of Medicine (Cronqvists stiftelse, reference SLS 934014); The Swedish Eye Foundation (reference 2020-04-27); The Swedish Cancer Society (20 0798 Fk)
• Keywords: VASCULOGENIC MIMICRY; tumor heterogeneity; DIGITAL IMAGE-ANALYSIS; PROGNOSIS; uveal melanoma; EVOLUTION; Oncology; CELLS; ASSAY; Science & Technology; BAP-1; Life Sciences & Biomedicine; survival
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology

Abstract

Malignant tumors are rarely homogenous on the morphological, genome, transcriptome or proteome level. In this study, we investigate the intratumor heterogeneity of BAP-1 expression in uveal melanoma with digital image analysis of 40 tumors. The proportion of BAP-1 positive cells was measured in full tumor sections, hot spots, cold spots and in scleral margins. The mean difference between hot spots and cold spots was 41 percentage points (pp, SD 29). Tumors with gene expression class 1 (associated with low metastatic risk) and 2 (high metastatic risk) had similar intratumor heterogeneity. Similarly, the level of intratumor heterogeneity was comparable in tumors from patients that later developed metastases as in patients that did not. BAP-1 measured in any tumor region added significant prognostic information to both American Joint Committee on Cancer (AJCC) tumor size category (p ≤ 0.001) and gene expression class (p ≤ 0.04). We conclude that there is substantial intratumor heterogeneity in uveal melanoma BAP-1 expression. However, it is of limited prognostic importance. Regardless of region, analysis of BAP-1 expression adds significant prognostic information beyond tumor size and gene expression class.