Utility of BRCA1-associated protein 1 immunoperoxidase stain to differentiate benign versus malignant mesothelial proliferations in cytologic specimens

Our plain-English summary of Utility of BRCA1-associated protein 1 immunoperoxidase stain to differentiate benign versus malignant mesothelial proliferations in cytologic specimens, by Z. McCroskey, G. Staerkel, S. Roy-Chowdhuri (Diagnostic Cytopathology, 2017).

The study

• Authors: Z. McCroskey, G. Staerkel, S. Roy-Chowdhuri
• Journal: Diagnostic Cytopathology
• Published: 2017;45(4):312-319
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Loss of BAP1 has recently been described as a highly specific marker for distinguishing malignant mesotheliomas (MM) from benign mesothelial proliferations (BMP). The aim of this study was to evaluate the utility of BAP1 in cytospin and cell block (CB) preparations.

Methods: We searched the database at our institution for cases of MM (n = 21) and BMP (n = 11). A Papanicolaou stained cytospin preparation and CB section from each case were selected for BAP1 staining. The results were scored as nuclear BAP1 staining, absent or present. Positive staining in non-neoplastic cells was noted as internal control.

Results: In the study group, MM cells showed a loss of BAP1 staining in 18/21(86%) cytospin and 19/21(90%) CB preparations. All cytospins showed appropriate positive nuclear staining in the "internal control" inflammatory cells. However, only 17/21(81%) of CB sections showed good internal control with positive nuclear staining in inflammatory cells. The intensity of BAP1 nuclear staining varied across cases. Overall, the intensity of staining was higher in cytospins, providing sharper contrast between the malignant cells with loss of stain and the benign inflammatory cells with retained stain in cases of MM. Sensitivity/specificity for cytospins when compared with CB was 86/100 and 88/100%, respectively.

Conclusions: Cytospin preparations have comparable sensitivity and specificity to CB with greater intensity and better contrast between negative and positive nuclei making the interpretation easier. We advise to interpret BAP1 IPOX stain results with caution with careful attention to staining of background nonmalignant "internal control" cells. Diagn. Cytopathol. 2017;45:312-319. © 2016 Wiley Periodicals, Inc.

© 2017 Wiley Periodicals, Inc.

In plain English

This retrospective study from MD Anderson Cancer Center, Houston, tested whether a BAP1 protein stain helps distinguish malignant mesothelioma from benign mesothelial growths in fluid samples. The authors stained cytospin and cell block slides from fluid samples of 21 patients with malignant mesothelioma and 11 with benign fluid. Mesothelioma cases came from a records search covering January 2006 to July 2015; benign-case dates were not given. Asbestos exposure was not studied. Tumor cells in the mesothelioma group lost BAP1 staining in 18 of 21 cytospins (86%) and 19 of 21 cell blocks (90%). Normal background inflammatory cells served as a check that the stain worked. In the mesothelioma group, these cells stained properly on all cytospins but only 17 of 21 cell blocks (81%), and only faintly in 12 of 21 cell blocks (57%). Counting only cases where this check worked, sensitivity and specificity were 86% and 100% for cytospins and 88% and 100% for cell blocks. The authors concluded that both methods performed similarly, that cytospins were easier to interpret, and that results need cautious interpretation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective diagnostic laboratory study comparing BAP1 immunoperoxidase staining on two types of cytology preparation (cytospin slides and cell blocks)
• Who was studied: Effusion (body-fluid) specimens at MD Anderson Cancer Center, Houston, Texas. The search for mesothelioma cases covered January 2006 to July 2015, although the Discussion mentions one specimen from 2005. Dates for the benign controls are not given. Study group: 21 patients with malignant mesothelioma (15 pleural fluid, 6 ascites). Nineteen had a tissue diagnosis of epithelioid malignant mesothelioma, and 2 had a clinical diagnosis whose tissue slides were not reviewed at the institution. Control group: 11 benign effusions (5 pleural fluid, 6 ascites) from patients with no history of mesothelioma.
• Exposure: No asbestos or other exposure was studied. What was tested was a stain for BAP1 protein on cytospin and cell block preparations. Asbestos is mentioned only in the introduction, as one of several factors implicated as a cause of malignant mesothelioma.
• Main results:
  • In the mesothelioma (study) group, tumor cells showed loss of BAP1 staining in 18/21 (86%) cytospin preparations and 19/21 (90%) cell block preparations.
  • In the mesothelioma group, background inflammatory cells (the internal control) stained properly on all cytospins but on only 17/21 (81%) cell block sections.
  • In the benign control group, BAP1 nuclear staining was retained in 10/11 (91%) cytospins and 11/11 (100%) cell blocks. The remaining cytospin had intense nonspecific background staining and was excluded from the sensitivity and specificity calculations.
  • In the mesothelioma group, background inflammatory cells in cell blocks had only faint BAP1 staining in 12/21 (57%) cases, often making interpretation difficult. The p value comparing background-cell staining on cytospins versus cell blocks in this group is printed as 'P 5 0.0025', where the 5 is a scanning error for an equals sign, so p = 0.0025.
  • Sensitivity and specificity of BAP1 loss for mesothelioma were 86% and 100% on cytospins and 88% and 100% on cell blocks. Only cases with good internal control staining were included in these calculations.
  • In one mesothelioma case, tumor cells showed strong nuclear BAP1 staining on the cytospin but were negative on the cell block. On re-review, the cell block's background cells had very faint to absent staining, which the authors said made the validity of the cell block staining questionable.
• The authors' conclusion: The authors concluded that cytospin preparations gave sensitivity and specificity similar to cell blocks. Although sensitivity was slightly higher on cell blocks, they found BAP1 results easier to interpret on cytospins because of greater staining intensity and contrast. They advised caution when interpreting BAP1 staining on cytology specimens, with careful attention to the staining of background non-malignant 'internal control' cells.
• Limitations the authors state:
  • None of the patients had genetic testing. The authors therefore could not exclude that weak staining reflected inherited (germline) BAP1 mutations.
  • None of the corresponding surgical tissue specimens had BAP1 staining, so there was no 'gold standard' for comparison.
  • Only the epithelioid type of mesothelioma was in the study group. The authors said this likely produced a higher sensitivity of BAP1 loss.
  • The authors suggested that the 'archival age' of older specimens and differences in specimen processing may have affected staining.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: BAP1, Malignant Mesothelioma, Cell Block.

Related studies

• BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations — M. Cigognetti, S. Lonardi, et al. (2015)
• Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens — K.B. Berg, A.M. Churg, et al. (2020)
• Diagnostic value of BRCA1-associated protein-1, glucose transporter-1 and desmin expression in the discrimination between reactive mesothelial proliferation and malignant mesothelioma in tissues and effusions — S. Önder, E. Özogul, et al. (2019)
• The value of BRCA-1-associated protein 1 expression and cyclin-dependent kinase inhibitor 2A deletion to distinguish peritoneal malignant mesothelioma from peritoneal location of carcinoma in effusion cytology specimens — W. Althakfi, S. Gazzo, et al. (2020)
• Loss of BRCA1-associated protein 1 (BAP1) expression is rare in non-small cell lung cancer — D. Owen, B.S. Sheffield, et al. (2017)
• Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens — H.C. Hwang, B.S. Sheffield, et al. (2016)

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