Loss of BAP1 Expression Is Very Rare in Pancreatic Ductal Adenocarcinoma

Abstract

BackgroundPancreatic cancer is both common and highly lethal and therefore new biomarkers or potential targets for treatment are needed. Loss of BRCA associated protein-1 (BAP1) expression has been found in up to a quarter of intrahepatic cholangiocarcinomas. Given the close anatomical relationship between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma, we therefore sought to investigate the frequency of loss of BAP1 expression in pancreatic ductal adenocarcinoma.MethodsThe records of the department of Anatomical Pathology Royal North Shore Hospital, Sydney, Australia, were searched for cases of pancreatic ductal adenocarcinoma diagnosed between 1992 and 2014 with material available in archived formalin fixed paraffin embedded tissue blocks. Immunohistochemistry for BAP1 was performed on tissue microarray sections and if staining was equivocal or negative it was confirmed on whole sections. Negative staining for BAP1 was defined as loss of expression in all neoplastic nuclei, with preserved expression in non-neoplastic cells which acted as an internal positive control.ResultsLoss of BAP1 expression was found in only 1 of 306 (0.33%) pancreatic ductal adenocarcinomas. This case was confirmed to demonstrate diffuse loss of expression throughout all neoplastic cells in multiple blocks, consistent with BAP1 loss being an early clonal event. All other cases demonstrated positive expression of BAP1.ConclusionWe conclude that, in contrast to intrahepatic cholangiocarcinoma, loss of expression of BAP1 occurs very rarely in pancreatic ductal adenocarcinoma. Therefore BAP1 inactivation is unlikely to be a frequent driver abnormality in pancreatic adenocarcinoma.

The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma

“…Two previous studies demonstrated infrequent BAP1 loss in PDAC ranging from 0.33 to 2.4% (46,47). Similarly, we found BAP1 loss in 2% of the human PDAC samples evaluated ( Supplementary Fig.…”

Diagnostic Utility of BAP1, EZH2 and Survivin in Differentiating Pleural Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia: Immunohistochemical Study

“…Though it was beyond the scope of the current study, yet we found it intriguing to review the literature to find out the frequency of BAP1 loss, Survivin and EZH2 positivity in other malignancies that might pose differential diagnostic challenges with EM. While BAP1 loss was very rare in breast carcinoma [ 28 ], pancreatic ductal adenocarcinoma [ 29 ], non-small cell lung cancer [ 30 ] and colorectal adenocarcinoma [ 31 ], EZH2 positivity, on the other hand, was detected in advanced metastatic non-small cell lung cancer [ 32 ], 50% of primary pancreatic adenocarcinoma [ 33 ], more than 73.7% of primary colorectal carcinoma [ 34 ] and 49.8% of primary breast cancer [ 35 ]. Survivin was expressed in the cytoplasm of tumor cells in 59.3% of breast cancer [ 36 ] and 76.9% of pancreatic adenocarcinoma [ 37 ].…”

Long-term survival of a patient with pancreatic cancer and lung metastasis: A case report and review of literature

“…In several types of cancer, such as clear-cell renal cell carcinoma, uveal melanoma, and colorectal cancer, the presence of mutations of the BAP1 gene is a herald of poor prognosis[ 21 ]. The frequency of BAP1 mutations occurring in PDAC is low, about 0.33%[ 22 ], and whether it contributes to the induction and progression of PC is still unclear. Raf1 rearrangement can consecutively activate the MAPK ( i.e.…”