Somatic BRCA1-associated protein 1 (BAP1) loss is an early and rare event in esophageal adenocarcinoma

Heike Loeser; Dirk Waldschmidt; Fabian Kuetting; Simon Schallenberg; Thomas Zander; Elfriede Bollschweiler; Arnulf Hoelscher; Katharina Weckermann; Patrick Plum; Hakan Alakus; Reinhard Buettner; Alexander Quaas

doi:10.3892/mco.2017.1286

Somatic BRCA1-associated protein 1 (BAP1) loss is an early and rare event in esophageal adenocarcinoma

Mol Clin Oncol. 2017 Aug;7(2):225-228. doi: 10.3892/mco.2017.1286. Epub 2017 Jun 8.

Affiliations

¹ Institute of Pathology, University of Cologne, D-50937 Cologne, Germany.
² Department of Gastrointestinal Diseases and Hepatology, University of Cologne, D-50937 Cologne, Germany.
³ Department of Oncology and Hematology, Center of Integrated Oncology, University of Cologne, Gastrointestinal Cancer Group Cologne (GCGC), D-50937 Cologne, Germany.
⁴ Department of Visceral Surgery, University of Cologne, Gastrointestinal Cancer Group Cologne (GCGC), D-50937 Cologne, Germany.

Abstract

Esophageal cancer is the eighth most common malignant tumor worldwide, and the number of incidences of esophageal adenocarcinoma is increasing in the Western world. Despite improvements in perioperative treatment, the overall survival rate of patients with esophageal adenocarcinoma remains poor. Breast cancer type 1 susceptibility protein (BRCA1)-associated protein (BAP1) is located on chromosome 3p21, and it is an enzyme with ubiquitin carboxyl hydrolase activity that regulates cell growth. It interacts with BRCA1, and the nuclear localization of BAP1 is required for its tumor suppressor function. BAP1 is frequently mutated in uveal melanomas, malignant mesothelioma and several carcinomas, including a subtype of renal cell carcinoma, intrahepatic cholangiocarcinoma and squamous cell carcinoma of the esophagus. Furthermore, several germline-associated mutations of tumors have been described (BAP1 hereditary cancer syndrome). However, the importance and frequency of BAP1 alterations in adenocarcinoma of the esophagus remain to be elucidated. In the present study, tissue microarrays of 332 resected adenocarcinomas (including a few cases of concomitant Barrett dysplasia) of the esophagus were constructed. The tumor tissue was analyzed using immunohistochemistry to investigate the levels of BAP1 expression. Fibroblasts or inflammatory cells served as an internal positive control. Three adenocarcinomas revealed nuclear loss of BAP1 (0.9%). One case with concomitant Barrett dysplasia also exhibited a loss of BAP1. Of the resected adenocarcinomas, 329 of them exhibited an intact and uniform strong nuclear staining pattern. To the best of our knowledge, this is the first description of BAP1 deficiency in adenocarcinomas of the esophagus. Furthermore, it has been demonstrated that BAP1 loss is possibly an early event in esophageal adenocarcinoma. These results warrant further functional and clinical evaluation.

Keywords: BRCA1-associated protein; breast cancer type 1 susceptibility protein; esophageal adenocarcinoma; immunohistochemistry; mutation; tumor suppressor.