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 × 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.

Mesothelioma: recent highlights

“…The most specific marker for mesothelioma is WT1. However, for peritoneal mesotheliomas in women, WT1 is not helpful as it stains ovarian cancers; instead ER and PR staining should be used (4,5).…”

Loss of BRCA1‐associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions

“…So far, the BAP1 antibody has been tested primarily on biopsies. [13][14][15][16][17][18][19][20] Only a few studies have used BAP1…”

Diagnostic and prognostic biomarkers for malignant mesothelioma: an update

“…However, differential diagnosis of MM is challenging, because MM morphology is similar to other cancers. In the epithelioid MM subtype morphology can be confused with that of non-small cell lung carcinomas, renal cell carcinomas, and others (19). The morphology of biphasic MMs can be similar to the one of synovial sarcomas and other biphasic malignancies, whilst sarcomatoid mesothelioma is often morphologically indistinguishable from other spindle cell tumors, including carcinosarcoma.…”

“…This diagnostic uncertainty is a serious and critical issue because patients with different cancers need different treatments and may have different prognosis. The accuracy of MM diagnosis has been improved by using a set of immunohistochemical (IHC) markers, including mesothelial markers (calretinin, the most sensitive, and WT-1, the most specific) and carcinoma-related markers (CEA, CD15, Ber-EP4, MOC-31, TTF-1) for differential diagnosis of carcinoma (19,20). It is by combining the results obtained with these markers together that a correct diagnosis can be obtained, because-as an example-calretinin and WT1 staining is not exclusively specific for MM, but can be found also in other malignancies.…”

“…Notably, these tumors are morphologically indistinguishable and both stain positively for WT1. However, although these IHC diagnostic tools are of undeniable help to diagnose correctly most MMs, there are still about 10% of cases in which the diagnosis remains dubious because, for example, in both MM and lung carcinoma markers result as either positive or negative, or only a fraction of tumor cells are positive (19). Moreover, in the absence of evident MM tumor cell invasion into the surrounding normal tissues, it is particularly challenging to distinguish atypical mesothelial hyperplasia from epithelioid type MM, as well as biphasic and sarcomatoid MM subtypes from organizing pleuritis (21,22).…”