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Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients

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Abstract

This study aims to determine whether a semi-quantitative assessment of inflammatory response in tumor and stroma on routine hematoxylin and eosin-stained (H&E) slides can predict survival in patients with epithelioid malignant pleural mesothelioma (MPM). H&E sections of 175 epithelioid MPM specimens from a single institution (1989–2009) were reviewed. Patients who received neoadjuvant chemotherapy were excluded from analysis. Each tumor was histologically assessed for acute and chronic inflammatory response both within the tumor and the stromal component. Inflammatory response was graded: low (none to mild infiltrate) or high (moderate to severe infiltrate). Log-rank test and Cox proportional hazards regression were used to investigate the association between the degree of inflammation (acute/tumor, acute/stroma, chronic/tumor, and chronic/stroma) and overall survival (OS). Patients with high chronic inflammatory response in stroma (n = 59) had improved survival compared to low (n = 116) (median OS = 19.4 vs. 15.0 months, P = 0.01). This prognostic stratification remained significant in stage III patients (median OS = 16.0 vs. 9.3 months, P = 0.03). In multivariate analysis, chronic inflammation in stroma was an independent predictor of survival (HR = 0.659, 95% CI 0.464–0.937, P = 0.02). While high degree of chronic inflammatory cell infiltration in the stromal component was associated with improved overall survival, degree of other inflammatory responses did not show significant correlation with OS. Our study for the first time investigates inflammatory response in tumor and stroma and not only suggests the prognostic value of inflammatory response in epithelioid MPM but also provides rationale for investigation of immunotherapy to benefit epithelioid MPM patients.

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Acknowledgments

We thank Joe Dycoco for his help with the mesothelioma database within the Division of Thoracic Surgery. This work was supported in part by Mesothelioma Applied Research Foundation (MARF) Grant in memory of Lance S. Ruble, Stony Wold-Herbert Fund, New York State Empire Clinical Research Investigator Program (ECRIP), American Association for Thoracic Surgery (AATS)—Third Edward D. Churchill Research Scholarship, IASLC—International Association for the Study of Lung Cancer Young Investigator Award, National Lung Cancer Partnership/LUNGevity Foundation Research Grant, William H. Goodwin and Alice Goodwin and the Commonwealth Foundation for Cancer Research and the Experimental Therapeutics Center.

Conflict of interest

All authors affirm that we have no actual or potential conflict of interest including any financial, personal, or other relationships with other people or organizations.

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Authors and Affiliations

  1. Division of Thoracic Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Kei Suzuki, Kyuichi Kadota & Valerie W. Rusch

  2. Department of Epidemiology & Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Camelia S. Sima

  3. Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Michel Sadelain

  4. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    William D. Travis

  5. Division of Thoracic Surgery, Department of Surgery, Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Prasad S. Adusumilli

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  1. Kei Suzuki
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Correspondence to Prasad S. Adusumilli.

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Suzuki, K., Kadota, K., Sima, C.S. et al. Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients. Cancer Immunol Immunother 60, 1721–1728 (2011). https://doi.org/10.1007/s00262-011-1073-8

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  • DOI: https://doi.org/10.1007/s00262-011-1073-8

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