Mesothelioma families without inheritance of a BAP1 predisposing mutation

Abstract

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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

“…When intense, cytoplasmic staining can obscure the true nature of nuclear signal and lead to interpretation errors. Cytoplasmic staining in MM has been reported up to 27% and explained by sequestration of some mutated BAP1 isoforms in the cytoplasm due to prevented nuclear localisation, resulting in loss of nuclear signal . Some authors have suggested that cytoplasmic BAP1 staining that is together with nuclear negativity could be associated with better prognosis .…”

“…21,24 We and most previous studies observed 100% specificity for prevented nuclear localisation, resulting in loss of nuclear signal. 26,27 Some authors have suggested that cytoplasmic BAP1 staining that is together with nuclear negativity could be associated with better prognosis. 26,28 Righi et al 28 showed that 100% of the MM cases with this type of reactivity were mutated, concluding that it is a reliable predictor of BAP1 mutation.…”

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

“…The reasons of this finding are not well defined. 19,29,30 One explanation is that somatic alterations in exons coding for nuclear localization signals led to BAP1 protein delocalization. 29 BAP1 cytoplasmic positivity could be used as positive control in cytological samples, when internal control cells are absent.…”

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

“…BAP1 has garnered both research and clinical focus in MPM based on its high rate of mutation, demonstrated role in other malignancies [2], and common use as an immunohistochemical biomarker for MPM diagnosis, particularly for the epithelioid subtype [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. The monoclonal antibody C4 (Santa Cruz Biotechnology, Dallas, TX, USA), utilized in most clinical and investigational settings [3,5,[7][8][9][10][11][12][15][16][17][18][19][20][21][22][23][25][26][27], binds within the C-terminal region of the BAP1 protein (aa 430-729). Clinical and research use involves binary evaluation of presence or absence of BAP1 nuclear staining, defined as positive when the nuclei of tumor cells exhibit immunoreactivity.…”

“…Most prior investigations utilized small numbers of samples [13][14][15]22,23,25,27,30]. Those including larger numbers have used biopsies [7,10,11,14,17,27], or tissue microarrays [8,12,16,19], including tumor samples insufficient to evaluate potential intra-tumoral heterogeneity of BAP1 staining [9,10,13,23,25]. The objective of the current study was to examine the immunohistochemical localization of BAP1 using clinical blocks from a large cohort of surgically resected MPM cases, of which 263 had BAP1 sequencing data.…”