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

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.

SUBMITTER: Suzuki K

PROVIDER: S-EPMC6250069 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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

Suzuki Kei K Kadota Kyuichi K Sima Camelia S CS Sadelain Michel M Rusch Valerie W VW Travis William D WD Adusumilli Prasad S PS

Cancer immunology, immunotherapy : CII 20110719 12

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 inflammat ...[more]

PMID: 21769693

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Project description:Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n=40), normal lung specimens (n=4), normal pleura specimens (n=5), and MPM and SV40-immortalized mesothelial cell lines (n=5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma which correlate loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (i.e. software) to create and explore complex physiological pathways that may be relevant in mesothelioma tumorigenesis, pathobiology, or both. Tissues and cell lines profiled using microarrays. Discarded MPM surgical specimens (n=40), normal pleura specimens (n=5), and normal lung specimens (n=4) were freshly collected (and snap frozen) from patients who underwent surgery at Boston's Brigham and Women's Hospital (BWH) between October 1998 and August 2000. All of these patients underwent extrapleural pneumonectomy with heated intra-pleural cisplatin chemotherapy delivered after the specimens were removed. All normal specimens were obtained from patients who were never diagnosed with MPM. Two human MPM cell lines (MS589 and MS428) were kindly provided by Jonathan A. Fletcher, M.D., Department of Pathology, BWH. The JMN1B MPM cell line19,20 has been described previously. The SV40-immortalized, non-tumorigenic mesothelial cell line (Met-5A)21 and the MPM cell line MSTO-211H22 were purchased from the American Type Culture Collection. Normal tissues were obtained from additional consented patients undergoing treatment for diseases other than MPM. All MPM samples used in these studies contained relatively pure tumor (greater than 50% tumor cells per high power field examined in a section adjacent to the tissue used). The microscopic slides from the patients' resection specimens were reviewed by one of the authors (J.G.), and the diagnosis and histologic subclassification of MPM confirmed in all cases. Linked clinical and pathological data were obtained for all patients who contributed tumor specimens. Specimens and data were rendered anonymous to protect patient confidentiality. Studies utilizing human tissues were approved by and conducted in accordance with the policies of the Institutional Review Board at BWH.

Dataset Information

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

Publications

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

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