High BIN1 expression has a favorable prognosis in malignant pleural mesothelioma and is associated with tumor infiltrating lymphocytes

Our plain-English summary of High BIN1 expression has a favorable prognosis in malignant pleural mesothelioma and is associated with tumor infiltrating lymphocytes, by T. Ahmadzada, K. Lee, C. Clarke, et al (Lung Cancer, 2019).

The study

• Authors: T. Ahmadzada, K. Lee, C. Clarke, W.A. Cooper, A. Linton, B. McCaughan, R. Asher, S. Clarke, G. Reid, S. Kao
• Journal: Lung Cancer
• Published: 2019;130:35-41
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Copyright © 2019 Elsevier B.V. All rights reserved.

In plain English

This retrospective study looked at tumor samples from 67 people with malignant pleural mesothelioma who had surgery (pleurectomy with decortication) at Royal Prince Alfred Hospital in Sydney between 1992 and 2007. The researchers stained the tumors for two proteins, BIN1 and IDO1, and for immune cells (CD3+ T cells, CD20+ B cells and CD68+ macrophages). They then compared these results with how long patients survived. The article does not report patients' asbestos exposure. Median survival for the whole group was 7.7 months (95% CI 5.6 to 9.8). High BIN1, meaning at least 89% of tumor cells stained, was found in 34 patients (51%). Their median survival was 12 months, compared with 6 months for patients with low BIN1. After adjusting for age, gender, tumor subtype, PD-L1, the blood neutrophil-to-lymphocyte ratio and tumor macrophages, the hazard ratio for high BIN1 was 0.39 (95% CI 0.18-0.82). IDO1 was not significantly associated with survival. Of the 65 tumors that could be classified, 50 (77%) had T cells inside the tumor, and this was significantly associated with high BIN1. The authors concluded that high BIN1 expression was a favorable prognostic factor in this disease.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of surgically removed tumor samples, stained by immunohistochemistry and compared with overall survival (Kaplan-Meier and Cox regression analyses)
• Who was studied: 67 patients with malignant pleural mesothelioma who had pleurectomy with decortication at Royal Prince Alfred Hospital, Sydney, Australia, between 1992 and 2007. 82% were male, the median age was 65, and 49% had the epithelioid subtype while 51% had non-epithelioid subtypes.
• Exposure: Asbestos exposure was not measured or reported. The factors studied were tumor markers: BIN1 and IDO1 expression in tumor cells, and tumor-infiltrating immune cells (CD3+ T cells, CD20+ B cells, CD68+ macrophages). These were related to previously published PD-L1 data and to the blood neutrophil-to-lymphocyte ratio.
• Main results:
  • Median overall survival for all 67 patients was 7.7 months (95% CI 5.6 to 9.8). One patient was still alive at the end of the study.
  • 20 patients (30%) had positive IDO1 expression (above 0%), and 34 patients (51%) had high BIN1 expression (89% or more of tumor cells).
  • Median overall survival was 12 months for patients with high BIN1 and 6 months for patients with low BIN1.
  • In unadjusted analysis, high BIN1 was significantly associated with better overall survival (HR 0.56; 95% CI 0.34-0.93; p = 0.03).
  • After adjustment for age, gender, histological subtype, PD-L1, NLR and CD68+ tumor macrophages, high BIN1 remained an independent prognostic factor (HR 0.39; 95% CI 0.18-0.82; p = 0.01).
  • IDO1 expression was not significantly associated with overall survival (Table 2: HR 0.73; 95% CI 0.43-1.25; p = 0.25).
  • High CD68+ macrophages in the tumor were associated with poorer overall survival in unadjusted analysis (median 6 vs 11 months, p = 0.04). In the adjusted model this was not statistically significant (Table 2: HR 1.77; 95% CI 0.81-3.85; p = 0.15).
  • A high blood neutrophil-to-lymphocyte ratio was associated with poorer overall survival in unadjusted analysis (median 6 vs 9 months, p = 0.03). In the adjusted model this was not statistically significant (Table 2: HR 0.68; 95% CI 0.30-1.52; p = 0.34).
  • Of the 65 tumors classified by immune phenotype (Table 1), 50 (77%) were immune inflamed (T cells inside the tumor), 13 (20%) were immune excluded and 2 (3%) were immune desert.
  • Tumor-infiltrating T cells were significantly associated with BIN1 (p less than 0.01). 93% of patients with high BIN1 had the immune inflamed phenotype.
  • No significant association was found between PD-L1 and BIN1 (p = 0.78), between PD-L1 and IDO1 (p = 0.56), or between IDO1 and BIN1 (p = 0.60).
• The authors' conclusion: The authors concluded that high BIN1 expression was a favorable prognostic factor in malignant pleural mesothelioma.
• Limitations the authors state:
  • The authors said the lack of a survival difference for IDO1, and the lack of an inverse relationship between IDO1 and BIN1, may have been due to the small number of IDO1-positive samples.
  • Median survival in this study (7.7 months) was lower than the roughly 12 months commonly reported. The authors attributed this possibly to the higher proportion of non-epithelioid tumors (51%) compared with about 30% generally reported.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Prognosis, Pleural Mesothelioma, Overall Survival, Immunohistochemistry, Pleurectomy/Decortication (P/D), Biomarker, Histological Subtype, PD-L1.

Related studies

• CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection — N. Yamada, S. Oizumi, et al. (2010)
• Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma — N. Sobhani, G. Roviello, et al. (2019)
• Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors — S. Hendry, R. Salgado, et al. (2017)
• Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans — M. Stapelberg, R. Zobalova, et al. (2014)
• ERCC1, MLH1, MSH2, MSH6, and βIII-tubulin: resistance proteins associated with response and outcome to platinum-based chemotherapy in malignant pleural mesothelioma — S. Ting, F.D. Mairinger, et al. (2013)
• Malignant mesothelioma-associated antigens recognized by tumor-infiltrating B cells and the clinical significance of the antibody titers — Y. Shigematsu, T. Hanagiri, et al. (2009)

Browse more research in Lung Cancer, or return to medical research.