Expression of BRCA1-associated protein 1 in primary tumors and metastasis in an animal model of uveal melanoma

Abstract

Background: Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Despite successful local treatment, approximately 50% of these patients develop lethal metastatic disease. BRCA1-associated protein 1 (BAP1) encodes BAP1, which functions as a tumor suppressor. Inactivation by a somatic mutation in BAP1 results in a loss of protein expression, which is associated with increased risk of metastasis. Aim: To analyze the expression of BAP1 protein in primary uveal tumors and their corresponding metastasis in an animal model of UM and to determine whether BAP1 expression is lost during the metastatic process. Subjects and Methods: Postmortem eyes and lungs with metastasis from nine rabbits previously inoculated with human UM cells expressing BAP1 (92.1 strain) were analyzed. Immunohistochemistry was performed on formalin-fixed paraffin-embedded samples using a monoclonal BAP1 (C-4) antibody. Expression was evaluated by the extent and intensity of staining. All primary tumors and metastasis were positive for BAP1. Results: The staining was diffuse and intense in the primary tumors of four rabbits (67%), focal-intense in one rabbit and focal-mild in one rabbit. All lung metastasis showed focal staining. All animals with intense BAP1 staining in the primary tumor showed mild BAP1 in the metastasis. Discussion: A predominant pattern observed between primary and metastatic lesion shows a transition from moderate into mild intensity and diffuse into the focal extent, suggesting a decrease in BAP1 expression. Future studies, including the human tissue of primary UM and their corresponding metastasis, should be performed to corroborate these findings.

Keywords

• animal model
• brca1-associated protein 1 mutation
• immunohistochemistry
• metastasis
• uveal melanoma