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BRCA1-Associated Protein 1 (BAP1) Immunohistochemical Expression as a Diagnostic Tool in Malignant Pleural Mesothelioma Classification: A Large Retrospective.

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Presentation on theme: "BRCA1-Associated Protein 1 (BAP1) Immunohistochemical Expression as a Diagnostic Tool in Malignant Pleural Mesothelioma Classification: A Large Retrospective."— Presentation transcript:

1 BRCA1-Associated Protein 1 (BAP1) Immunohistochemical Expression as a Diagnostic Tool in Malignant Pleural Mesothelioma Classification: A Large Retrospective Study  Luisella Righi, MD, PhD, Eleonora Duregon, MD, PhD, Simona Vatrano, BSc, Stefania Izzo, MLT, Jessica Giorcelli, MLT, Milena Rondón-Lagos, BSc, PhD, Valeria Ascoli, MD, Enrico Ruffini, MD, Laura Ventura, MD, Marco Volante, MD, Mauro Papotti, MD, Giorgio Vittorio Scagliotti, MD  Journal of Thoracic Oncology  Volume 11, Issue 11, Pages (November 2016) DOI: /j.jtho Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

2 Figure 1 Schematic representation of main clinical and pathological features in 143 malignant pleural mesothelioma cases. BIO, biopsies; EPI, epithelioid; BIPH, biphasic; SARCO, sarcomatous; NA, not applicable; IHC, immunohistochemistry; POS, positive; NEG, negative. Nuclear grading score according to Kadota et al.12 Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

3 Figure 2 (A) Epithelioid malignant pleural mesothelioma (MPM) with scant associated stroma. (B) Epithelioid MPM with relevant associated stromal component with low to moderate atypia in the spindle cells. (C) Epithelioid MPM with relevant associated stromal component with severe atypia in the spindle cells. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

4 Figure 3 (A) Epithelioid malignant pleural mesothelioma showing nuclear BRCA1-associated protein 1 (BAP1) immunonegativity in neoplastic and nuclear BAP1 immunopositivity in associated nonneoplastic cells (internal control). (B) Epithelioid malignant pleural mesothelioma showing BAP1 cytoplasmic immunopositivity and nuclear negativity in neoplastic cells. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

5 Figure 4 (A) Epithelioid malignant pleural mesothelioma (MPM) showing nuclear BRCA1-associated protein 1 (BAP1) immunonegativity in neoplastic cells and BAP1 positivity in atypical stromal cells (insert: high power). (B) Pleomorphic MPM showing nuclear BAP1 immunonegativity in neoplastic cells and nuclear BAP1 immunopositivity in stromal associated cells. (C) Sarcomatoid MPM showing heterogeneous BAP1 immunoreactivity in malignant spindle cells (thick arrow indicates BAP1-positive atypical spindle cell; thin arrow indicates BAP1-negative atypical spindle cell). Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

6 Figure 5 (Upper panels) Malignant pleural mesothelioma case with epithelioid neoplastic and atypical stromal component. (A) Epithelioid component (blue square) was microdissected and analyzed for BRCA1-associated protein 1 (BAP1 protein) and BRCA1-associated protein 1 gene (BAP1) status. (B) BAP1 immunonegativity of the epithelioid component with positive internal control; (insert) electropherogram of the BAP1 mutational analysis showing the presence of a point mutation. (C) Atypical stromal component (red square) was microdissected and analyzed for BAP1 protein and BAP1 gene status. (D) BAP1 immunopositivity of the stromal component; (insert) electropherogram of the BAP1 mutational analysis showing a wild-type status. (Lower panel) In the table the mutational analysis results of biphasic malignant pleural mesothelioma cases with differential BAP1 immunohistochemical expression analyzed separately in the epiothelioid and stromal components. E, epithelioid; S, sarcomatous; IHC, immunohistochemical; POS, positive; NEG, negative; mut, mutation; WT, wild type; NA, not annotated. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

7 Figure 6 (A) Survival curves of malignant pleural mesothelioma (MPM) main histological subtypes. (B) Survival curves of pleomorphic MPM cases compared with biphasic and epithelioid MPM. (C) Survival curves of nuclear grade groups according to Kadota et al12 in MPM with epithelioid component (biphasic type included). (D) Survival curves of stromal grade groups. (E) Paired comparison between epithelial and stromal grading score groups. (F) Survival curves of different BRCA1-associated protein 1 immunohistochemical pattern groups. (G) Survival curves of BRCA1-associated protein 1 immunohistochemical expression–positive and immunohistochemical expression–negative (including cytoplasmic positive) groups. EPI, epithelioid; BIPH, biphasic; SARCO, sarcomatous; PLEO, pleomorphic MPM; mod, moderate; POS, positive; NEG, negative; CYTO, cytoplasmic. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

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