Questioning the prognostic role of BAP-1 immunohistochemistry in malignant pleural mesothelioma: A single center experience with systematic review and meta-analysis

Cantini, Luca; Pecci, Federica; Murrone, Alberto; Tomasetti, Marco; Copparoni, Cecilia; Fiordoliva, Ilaria; Morgese, Francesca; Rinaldi, Silvia; Mazzanti, Paola; Rubini, Corrado; Cimadamore, Alessia; Barbisan, Francesca; Scarpelli, Marina; Santarelli, Lory; Berardi, Rossana

doi:10.1016/j.lungcan.2020.06.024

Cited by 11 publications

(13 citation statements)

References 42 publications

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“…Since IHC on tumor tissue does not help to distinguish between somatic and germline mutations, the clinic relevance of somatic BAP1 loss-of-function in MPM remains under debate, with conflicting reports that it may be associated with epithelioid subtype (19,30). In accordance with our previous meta-analysis, the significant association of BAP1 loss with OS found in MPM was lost in multivariate analysis showing that the histological subtype mainly affected the patient survival (31). We also confirmed that BAP1 loss is more frequent in epithelioid histotype, as previously observed (32)(33)(34).…”

Section: Discussionsupporting

confidence: 80%

BRCA-associated protein 1 (BAP1) and miR-31 combination predicts outcomes in epithelioid malignant pleural mesothelioma

Murrone¹,

Cantini²,

Pecci³

et al. 2021

J Thorac Dis

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Background: Malignant pleural mesothelioma (MPM) is an aggressive disease, with few available treatment options. Identification of novel prognostic and predictive biomarkers is a priority. In MPM patients, BRCA-associated protein 1 (BAP1) alterations are detected in about 60% of cases and miR-31 seems to be involved in BAP1 regulation at post-transcriptional level. The aim of this study was to evaluate the interaction between BAP1 and miR-31 in MPM and their prognostic role in MPM. Methods: The expression of BAP1 and miR-31 was analyzed in tissues of 55 MPM patients treated with first-line chemotherapy. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier method and Log-rank test was used to investigate differences among subgroups. Multivariate Cox regression analysis was used to evaluate independent predictors of survival. Results: In the whole cohort, loss of BAP1 was associated with a significant improvement in OS, but not in PFS. Lower miR-31 levels were detected in epithelioid MPM (e-MPM) compared to the non-epithelioid subtypes and resulted associated with BAP1 loss. By looking at the e-MPM subgroup, loss of BAP1 was not able to predict clinical outcome. Conversely, miR-31 levels were significantly associated with PFS (P=0.028), but not with OS (P=0.059). By combining the two biomarkers, e-MPM patients with BAP1 loss/low miR-31 levels showed a better prognosis compared to the ones with BAP1 retained/high miR-31 levels (median OS 22.6 vs. 17.0 months, P=0.017 and median PFS 8.7 vs. 5.1 months, P=0.020). The BAP1 and miR-31 combination was confirmed at multivariate analysis as an independent prognostic factor for e-MPM patients.Conclusions: In this preliminary study, we found that the prognostic stratification of e-MPM patients may be improved by simultaneously assessing of BAP1 status and miR-31 levels. The two-biomarker score is useful to identify a subgroup of e-MPM tumors characterized by BAP1 retained and high miR-31 levels with worse clinical outcome.

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Section: Discussionsupporting

confidence: 80%

BRCA-associated protein 1 (BAP1) and miR-31 combination predicts outcomes in epithelioid malignant pleural mesothelioma

Murrone¹,

Cantini²,

Pecci³

et al. 2021

J Thorac Dis

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“…Many studies have evaluated the correlation of BAP1 status by IHC and prognosis and have had mixed results, although most have found no significant association with survival after adjusting for known prognostic indicators. 4,16,18,25,[37][38][39][40] This lack of consistency may be due to many factors, including small number of patients, lack of validation, heterogeneity in patient selection, study size, patient management, and the adjustment, or lack thereof, within these studies for known prognostic indicators. In this study, we have revealed that BAP1 is a predictive marker in platinum and pemetrexed, nonsurgical PM patients in both the Danish and Australian cohorts, independent of other prognostic markers such as age, sex, ECOG PS, and histological subtype.…”

Section: Discussionmentioning

confidence: 99%

“…[20][21][22][23][24] Few studies have specifically evaluated the association of BAP1 IHC status with platinum and pemetrexed treatment. 14,25,26 On the basis of the biological function of BAP1 and longer survival in treated patients with BAP1 germline mutation, we postulated that loss of BAP1 in the tumor may predict survival after platinum and pemetrexed treatment in a general PM cohort.…”

Section: Introductionmentioning

confidence: 99%

BAP1 Loss by Immunohistochemistry Predicts Improved Survival to First-Line Platinum and Pemetrexed Chemotherapy for Patients With Pleural Mesothelioma: A Validation Study

Louw

Panou

Szejniuk

et al. 2022

Journal of Thoracic Oncology

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“…A high-risk germline mutation in the BAP1 gene has been previously reported for MM, with somatic BAP1 mutations found to be latent in more than 20% of MM patients 11 , 12 . In addition to BAP1 loss 13 , MTAP (methylthioadenosine phosphorylase) loss help diagnose mesothelioma tumorigenesis 6 , 9 , 14 , 15 . NF2 has also been a target molecule for MM therapy 16 .…”

Section: Introductionmentioning

confidence: 99%

RhoA and vigilin are candidates for immunohistochemical markers for epithelioid malignant mesothelioma

Hiratsuka

Yamamoto

Yoshizawa

et al. 2022

Sci Rep

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Diagnostic markers of malignant mesothelioma (MM) have been extensively investigated. Immunohistochemistry (IHC) markers, such as calretinin, have been used for pathologic diagnosis. However, more diagnostic markers are required to improve the specificity and sensitivity of pathologic diagnosis. This study proposed two proteins as diagnostic markers for epithelioid MM. One is RhoA, an MM mutation-susceptible locus-derived protein, and another is vigilin, a lung small cell carcinoma marker. IHC was performed using 93 MM (epithelioid, 71 cases; sarcomatoid, 13 cases; and biphasic, 9 cases), 64 lung adenocarcinoma (LAC), 60 lung squamous cell carcinoma (LSC), and 14 normal mesothelial (NM) tissues. The majority of epithelioid MM cases were positive for both RhoA and vigilin, whereas both IHCs showed lower stainability in biphasic and sarcomatoid MM. Besides, both IHCs showed significantly higher stainability for RhoA and vigilin in epithelioid MM than in LAC and LSC (p < 0.05). Chi-square tests showed that both RhoA and vigilin IHC positive rate in epithelioid MM was not significantly different from that of calretinin (p > 0.05). In the differential diagnosis of MM from lung cancer, the accuracy and specificity of RhoA, vigilin, and calretinin staining were almost equivalent. Further, H-score test showed that there was no significant difference between RhoA versus calretinin and vigilin versus calretinin in IHC positivity in epithelioid MM (p > 0.05). In conclusion, RhoA and vigilin may be candidates for immunohistochemical markers for epithelioid MM.

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Questioning the prognostic role of BAP-1 immunohistochemistry in malignant pleural mesothelioma: A single center experience with systematic review and meta-analysis

Cited by 11 publications

References 42 publications

BRCA-associated protein 1 (BAP1) and miR-31 combination predicts outcomes in epithelioid malignant pleural mesothelioma

BRCA-associated protein 1 (BAP1) and miR-31 combination predicts outcomes in epithelioid malignant pleural mesothelioma

BAP1 Loss by Immunohistochemistry Predicts Improved Survival to First-Line Platinum and Pemetrexed Chemotherapy for Patients With Pleural Mesothelioma: A Validation Study

RhoA and vigilin are candidates for immunohistochemical markers for epithelioid malignant mesothelioma

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