Immunohistochemical Assessment of BAP1 Protein in Mucoepidermoid Carcinomas

Abstract

Mucoepidermoid carcinomas are common malignant salivary gland tumors. Despite recent advances in diagnosis and treatment, there has not been much improvement in outcome of these patients, necessitating identification of novel targeted therapeutic agents. Genomic profiling of mucoepidermoid carcinomas has recently revealed aberrations in BAP1 gene. Therefore, we conducted this study to identify BAP1 loss by immunohistochemistry in these tumors. Mucoepidermoid carcinoma cases were retrieved; hematoxylin-and-eosin stained sections were reviewed. Immunohistochemistry for BAP1 was performed. Forty cases were assessed, including 25 salivary gland and 15 pulmonary mucoepidermoid carcinomas. There were 19 cases in the parotid (76%), two in submandibular gland (8%), and remaining 16% from minor salivary gland locations. Ten (40%) were low grade, nine (36%) were intermediate grade, and six (24%) were high grade mucoepidermoid carcinomas. Thirteen (86.7%) pulmonary mucoepidermoid carcinomas were tracheobronchial, while two (13.3%) were intraparenchymal; all were low grade mucoepidermoid carcinomas. On immunohistochemistry, BAP1 nuclear staining was retained in all cases (100%), irrespective of tumor location or grade. Therapeutic connotations necessitate the identification of readily applicable techniques to detect BAP1 loss in mucoepidermoid carcinomas. Using immunohistochemistry, loss of BAP1 staining was not seen in any of our cases, suggesting insensitivity of BAP1 IHC to detect aberrations at genomic level in these tumors. Analysis of BAP1 alterations by targeted sequencing may therefore be performed prior to excluding the possibility of response to BAP1-targeted therapeutics based on immunohistochemistry alone.

Keywords: BAP1; Bronchopulmonary tumor; Mucoepidermoid carcinoma; Parotid; Salivary gland tumor.

Fig. 1

BAP1 staining in MECs: Case of submandibular high grade MEC (a HE, × 100) with retained BAP1 staining in squamoid, intermediate and mucous cells (d IHC, × 200). Case of parotid MEC, intermediate grade (c HE, × 100), with retained BAP1 expression in solid as well as cystic components (d IHC, × 100). Case of endobronchial low grade MEC (e HE, × 100) showing nuclear BAP1 positivity in tumor cells (f IHC, × 200)