Tamkin Ahmadzada1, Kenneth Lee2, Candice Clarke3, Wendy A Cooper4, Anthony Linton5, Brian McCaughan6, Rebecca Asher7, Stephen Clarke8, Glen Reid9, Steven Kao10. 1. Sydney Medical School, The University of Sydney, Australia. Electronic address: tahm4852@uni.sydney.edu.au. 2. Sydney Medical School, The University of Sydney, Australia; Department of Anatomical Pathology, Concord Repatriation General Hospital, Australia. 3. Department of Anatomical Pathology, Concord Repatriation General Hospital, Australia. 4. Sydney Medical School, The University of Sydney, Australia; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Australia; School of Medicine, Western Sydney University, Sydney, NSW, Australia. 5. Sydney Medical School, The University of Sydney, Australia; Department of Medical Oncology, Concord Repatriation General Hospital, Australia. 6. Sydney Cardiothoracic Surgeons, Australia. 7. NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia. 8. Sydney Medical School, The University of Sydney, Australia; Department of Medical Oncology, Royal North Shore Hospital, Australia. 9. Sydney Medical School, The University of Sydney, Australia; Asbestos Diseases Research Institute, Sydney, NSW, Australia; Department of Pathology, University of Otago, Dunedin, New Zealand. 10. Sydney Medical School, The University of Sydney, Australia; Asbestos Diseases Research Institute, Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, NSW, Australia.
Abstract
OBJECTIVES: A number of key immune regulators show prognostic value in malignant pleural mesothelioma (MPM), but the association between Bridging integrator 1 (BIN1), indoleamine 2,3 dioxygenase 1 (IDO1) and patient outcome has not been investigated. We aimed to determine the expression of BIN1 and IDO1, their association with other markers and impact on overall survival (OS) in MPM. MATERIALS AND METHODS: The expression of BIN1, IDO1, CD3, CD20 and CD68 were evaluated by immunohistochemistry in 67 patients who underwent pleurectomy/decortication. Survival analyses were performed using the Kaplan Meier method and significant biomarkers were entered into a Cox Regression multivariate model, accounting for known prognostic factors such as age, gender, histological subtype, PD-L1 expression and neutrophil-to-lymphocyte ratio. RESULTS: Immune markers were variably expressed in tumor cells, ranging from 0% to 100% for BIN1 (median: 89%), and 0% to 77.5% for IDO1 (median: 0%). Expression of markers of tumor-infiltrating lymphocytes (TILs) and macrophages ranged from 0% to more than 50%. BIN1 expression was high in 35 patients (51%) and was associated with increased OS (median: 12 vs 6 months for high and low BIN1 respectively,p = 0.03). Multivariate analysis showed BIN1 remained an independent prognostic indicator (HR 0.39; 95% CI: 0.18-0.82, p = 0.01). The majority of patients had immune inflamed tumors (77%) and there was a significant association between TILs and BIN1 (p = 0 < 0.01), PD-L1 (p=0.04) and CD68+ macrophages in the tumor (p < 0.01). There were no significant associations between PD-L1 and BIN1 or IDO1. CONCLUSION: High BIN1 expression is a favorable prognostic biomarker and is associated with TILs in MPM.
OBJECTIVES: A number of key immune regulators show prognostic value in malignant pleural mesothelioma (MPM), but the association between Bridging integrator 1 (BIN1), indoleamine 2,3 dioxygenase 1 (IDO1) and patient outcome has not been investigated. We aimed to determine the expression of BIN1 and IDO1, their association with other markers and impact on overall survival (OS) in MPM. MATERIALS AND METHODS: The expression of BIN1, IDO1, CD3, CD20 and CD68 were evaluated by immunohistochemistry in 67 patients who underwent pleurectomy/decortication. Survival analyses were performed using the Kaplan Meier method and significant biomarkers were entered into a Cox Regression multivariate model, accounting for known prognostic factors such as age, gender, histological subtype, PD-L1 expression and neutrophil-to-lymphocyte ratio. RESULTS: Immune markers were variably expressed in tumor cells, ranging from 0% to 100% for BIN1 (median: 89%), and 0% to 77.5% for IDO1 (median: 0%). Expression of markers of tumor-infiltrating lymphocytes (TILs) and macrophages ranged from 0% to more than 50%. BIN1 expression was high in 35 patients (51%) and was associated with increased OS (median: 12 vs 6 months for high and low BIN1 respectively,p = 0.03). Multivariate analysis showed BIN1 remained an independent prognostic indicator (HR 0.39; 95% CI: 0.18-0.82, p = 0.01). The majority of patients had immune inflamed tumors (77%) and there was a significant association between TILs and BIN1 (p = 0 < 0.01), PD-L1 (p=0.04) and CD68+ macrophages in the tumor (p < 0.01). There were no significant associations between PD-L1 and BIN1 or IDO1. CONCLUSION: High BIN1 expression is a favorable prognostic biomarker and is associated with TILs in MPM.
Authors: Tamkin Ahmadzada; Wendy A Cooper; Mikaela Holmes; Annabelle Mahar; Helen Westman; Anthony J Gill; Ina Nordman; Po Yee Yip; Abhijit Pal; Rob Zielinski; Nick Pavlakis; Adnan Nagrial; Dariush Daneshvar; Daniel Brungs; Deme Karikios; Vesna Aleksova; Juliet Burn; Rebecca Asher; Georges E Grau; Elham Hosseini-Beheshti; Glen Reid; Stephen Clarke; Steven Kao Journal: JTO Clin Res Rep Date: 2020-07-16