Positive nuclear BAP1 immunostaining helps differentiate non-small cell lung carcinomas from malignant mesothelioma

Abstract

The differential diagnosis between pleural malignant mesothelioma (MM) and lung cancer is often challenging. Immunohistochemical (IHC) stains used to distinguish these malignancies include markers that are most often positive in MM and less frequently positive in carcinomas, and vice versa. However, in about 10-20% of the cases, the IHC results can be confusing and inconclusive, and novel markers are sought to increase the diagnostic accuracy.We stained 45 non-small cell lung cancer samples (32 adenocarcinomas and 13 squamous cell carcinomas) with a monoclonal antibody for BRCA1-associated protein 1 (BAP1) and also with an IHC panel we routinely use to help differentiate MM from carcinomas, which include, calretinin, Wilms Tumor 1, cytokeratin 5, podoplanin D2-40, pankeratin CAM5.2, thyroid transcription factor 1, Napsin-A, and p63. Nuclear BAP1 expression was also analyzed in 35 MM biopsies. All 45 non-small cell lung cancer biopsies stained positive for nuclear BAP1, whereas 22/35 (63%) MM biopsies lacked nuclear BAP1 staining, consistent with previous data. Lack of BAP1 nuclear staining was associated with MM (two-tailed Fisher's Exact Test, P = 5.4 x 10-11). Focal BAP1 staining was observed in a subset of samples, suggesting polyclonality. Diagnostic accuracy of other classical IHC markers was in agreement with previous studies. Our study indicated that absence of nuclear BAP1 stain helps differentiate MM from lung carcinomas. We suggest that BAP1 staining should be added to the IHC panel that is currently used to distinguish these malignancies.

Keywords: BAP1; differential diagnosis; immunohistochemistry; lung cancer; mesothelioma.

Figure 1. Immunohistochemical characterization of non-small cell lung cancers

Representative lung adenocarcinoma (left) and SCC (right) were stained with Hematoxylin and Eosin, and for expression of BAP1, calretinin, CAM5.2, WT1, CK5, D2-40, p63, Napsin-A and TTF-1. Note the strong BAP1 nuclear staining in both specimens. All photomicrographs were taken at 400x original magnification; representative size bar is shown on the bottom right panel.

Figure 2. Immunohistochemical characterization of malignant mesotheliomas

Representative epithelioid (left), biphasic (center) and sarcomatoid (right) specimens were stained with Hematoxylin and Eosin, and for expression of BAP1, calretinin, CAM5.2, WT1, CK5, D2-40, p63, Napsin-A and TTF-1. Inserts depict the spindle component within the biphasic tumor. Note lack of BAP1 nuclear staining in the epithelioid and sarcomatoid specimens. All photomicrographs were taken at 400x original magnification; representative size bar is shown on the bottom right panel.