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Large-scale analysis of BAP1 expression reveals novel associations with clinical and molecular features of malignant pleural mesothelioma.

Publication ,  Journal Article
De Rienzo, A; Chirieac, LR; Hung, YP; Severson, DT; Freyaldenhoven, S; Gustafson, CE; Dao, NT; Meyerovitz, CV; Oster, ME; Jensen, RV; Yeap, BY ...
Published in: The Journal of pathology
January 2021

BRCA1-associated protein-1 (BAP1) expression is commonly lost in several tumors including malignant pleural mesothelioma (MPM). Presence or absence of immunohistochemical BAP1 nuclear staining in tumor cells is currently used for differential diagnosis of MPM. In this study, a large cohort of 596 MPM tumors with available clinical data was analyzed to examine associations of BAP1 staining pattern with clinical and molecular features that may reflect the impact of BAP1 mutation on MPM biology. Cases were classified according to the BAP1 staining pattern of tumor cells. Exome and RNA-sequencing data were available for subsets of cases. Levels of mRNA encoding claudin 15 (CLDN15) and vimentin (VIM) were determined using RT-qPCR on 483 cases to estimate the relative proportions of epithelial-like and mesenchymal-like components in each tumor. Four BAP1 staining patterns were observed: single-pattern nuclear staining (36%), single-pattern cytoplasmic staining (25%), single-pattern absent staining (12%), and combinations of these staining patterns (27%). This study confirmed prior reports that nuclear BAP1 is more frequently associated with wild-type BAP1 and sarcomatoid histology. However, no associations between BAP1 staining pattern(s) and mutations in specific protein domains and/or mutation type were observed. BAP1 staining patterns were significantly associated (p < 0.001) with BAP1 gene expression, MPM histologic subtypes, molecular clusters, and markers of epithelial-to-mesenchymal transition. Frequent observation of combinations of BAP1 staining patterns in MPM tumors indicated intra-tumoral heterogeneity of BAP1 status. Cytoplasmic BAP1 staining was identified as a putative indicator of favorable prognosis in non-epithelioid MPM. In conclusion, novel significant associations among different BAP1 staining patterns and subgroups of MPM tumors were observed, suggesting that the role of BAP1 in tumor progression may be more complex than its presumed tumor suppressor function. Cytoplasmic staining was identified as a putative indicator of favorable prognosis in non-epithelioid MPM, potentially addressing a critical need in clinical decision-making in this disease. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

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Published In

The Journal of pathology

DOI

EISSN

1096-9896

ISSN

0022-3417

Publication Date

January 2021

Volume

253

Issue

1

Start / End Page

68 / 79

Related Subject Headings

  • Young Adult
  • Ubiquitin Thiolesterase
  • Tumor Suppressor Proteins
  • Prognosis
  • Pleural Neoplasms
  • Pathology
  • Mutation
  • Middle Aged
  • Mesothelioma, Malignant
  • Male
 

Citation

APA
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ICMJE
MLA
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De Rienzo, A., Chirieac, L. R., Hung, Y. P., Severson, D. T., Freyaldenhoven, S., Gustafson, C. E., … Richards, W. G. (2021). Large-scale analysis of BAP1 expression reveals novel associations with clinical and molecular features of malignant pleural mesothelioma. The Journal of Pathology, 253(1), 68–79. https://doi.org/10.1002/path.5551
De Rienzo, Assunta, Lucian R. Chirieac, Yin P. Hung, David T. Severson, Samuel Freyaldenhoven, Corinne E. Gustafson, Nhien T. Dao, et al. “Large-scale analysis of BAP1 expression reveals novel associations with clinical and molecular features of malignant pleural mesothelioma.The Journal of Pathology 253, no. 1 (January 2021): 68–79. https://doi.org/10.1002/path.5551.
De Rienzo A, Chirieac LR, Hung YP, Severson DT, Freyaldenhoven S, Gustafson CE, et al. Large-scale analysis of BAP1 expression reveals novel associations with clinical and molecular features of malignant pleural mesothelioma. The Journal of pathology. 2021 Jan;253(1):68–79.
De Rienzo, Assunta, et al. “Large-scale analysis of BAP1 expression reveals novel associations with clinical and molecular features of malignant pleural mesothelioma.The Journal of Pathology, vol. 253, no. 1, Jan. 2021, pp. 68–79. Epmc, doi:10.1002/path.5551.
De Rienzo A, Chirieac LR, Hung YP, Severson DT, Freyaldenhoven S, Gustafson CE, Dao NT, Meyerovitz CV, Oster ME, Jensen RV, Yeap BY, Bueno R, Richards WG. Large-scale analysis of BAP1 expression reveals novel associations with clinical and molecular features of malignant pleural mesothelioma. The Journal of pathology. 2021 Jan;253(1):68–79.
Journal cover image

Published In

The Journal of pathology

DOI

EISSN

1096-9896

ISSN

0022-3417

Publication Date

January 2021

Volume

253

Issue

1

Start / End Page

68 / 79

Related Subject Headings

  • Young Adult
  • Ubiquitin Thiolesterase
  • Tumor Suppressor Proteins
  • Prognosis
  • Pleural Neoplasms
  • Pathology
  • Mutation
  • Middle Aged
  • Mesothelioma, Malignant
  • Male