Agnes Bilecz1, Paul Stockhammer2,3, Dirk Theegarten4, Izidor Kern5, Marko Jakopovic6, Miroslav Samarzija6, Thomas Klikovits3, Mir A Hoda3, Balázs Döme3,7,8, Felicitas Oberndorfer9, Leonhard Muellauer9, János Fillinger10, Ildikó Kovács7, Christine Pirker11, Martin Schuler12, Till Plönes2, Clemens Aigner2, Walter Klepetko3, Walter Berger11, Luka Brcic13, Viktória Laszlo3, Balazs Hegedus1,2. 1. 2nd Institute of Pathology, Semmelweis University, Budapest, Hungary. 2. Department of Thoracic Surgery, Ruhrlandklinik, University Duisburg-Essen, Essen, Germany. 3. Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University Vienna, Vienna, Austria. 4. Institute of Pathology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 5. University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia. 6. Department for Respiratory Diseases Jordanovac, University Hospital Center, University of Zagreb, Zagreb, Croatia. 7. Department of Tumor Biology, National Koranyi Institute of Pulmonology, Semmelweis University, Budapest, Hungary. 8. Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Vienna, Austria. 9. Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria. 10. Department of Pathology, National Koranyi Institute of Pulmonology, Semmelweis University, Budapest, Hungary. 11. Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine, Medical University of Vienna, Vienna, Austria. 12. Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 13. Medical University of Graz, Diagnostic and Research Institute of Pathology, Graz, Austria.
Abstract
AIMS: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the epithelioid type is associated with a more favourable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study. METHODS AND RESULTS: Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtyped. Nuclear grading and mitosis-necrosis score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis-necrosis score. The mitosis-necrosis score was a robust and independent prognostic factor in our patient cohort. The prognostic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours. CONCLUSIONS: Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.
AIMS: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the epithelioid type is associated with a more favourable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study. METHODS AND RESULTS: Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtyped. Nuclear grading and mitosis-necrosis score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis-necrosis score. The mitosis-necrosis score was a robust and independent prognostic factor in our patient cohort. The prognostic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours. CONCLUSIONS: Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.