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COPPS, a composite score integrating pathological features, PS100 and SDHB losses, predicts the risk of metastasis and progression-free survival in pheochromocytomas/paragangliomas

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Abstract

Current histoprognostic parameters and prognostic scores used in paragangliomas and pheochromocytomas do not adequately predict the risk of metastastic progression and survival. Here, using a series of 147 cases of paraganglioma and pheochromocytoma, we designed and evaluated the potential of a new score, the COPPS (COmposite Pheochromocytoma/paraganglioma Prognostic Score), by taking into consideration three clinico-pathological features (including tumor size, necrosis, and vascular invasion), and the losses of PS100 and SDHB immunostain to predict the risk of metastasis. We compared also the performance of the COPPS with several presently used histoprognostic parameters in risk assessment of these tumors. A PASS score (Pheochromocytoma of the Adrenal gland Scaled Score) ≥ 6 was significantly associated with the occurrence of metastases (P < 0.0001) and shorter PFS (P = 0.013). In addition, both MCM6 and Ki-67 LI correlated with worse PFS (P = 0.004 and P < 0.0001, respectively), and MCM6, but not Ki-67, was significantly higher in metastatic group (P = 0.0004). Loss of PS100 staining correlated with the occurrence of metastasis (P < 0.0001) and shorter PFS (P < 0.0001). At a value of greater or equal to 3, the COPPS correlated with shorter PFS (P < 0.0001), and predicted reproducibly (weighted Kappa coefficient, 0.863) the occurrence of metastases with a sensitivity of 100.0% and specificity of 94.7%. It thus surpassed those found for either PASS, SDHB, MCM6, or Ki-67 alone. In conclusion, while validation is still necessary in independent confirmatory cohorts, COPPS could be of great potential for the risk assessment of metastasis and progression in paragangliomas and pheochromocytomas.

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Acknowledgements

The authors thank the entire team of the Department of Pathology (CHRU, Nancy, France) for technical support and Bertrand HOUCHOT for manuscript editing.

Author information

Author notes

  1. Guillaume Gauchotte and Hélène Busby-Venner contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, CHRU de Nancy, Université de Lorraine, F-54000, Nancy, France

    Charlie Pierre, Antoine Max, Celso Pouget, Jean-Michel Vignaud, Guillaume Gauchotte & Hélène Busby-Venner

  2. Department of Medical Gynecology, CHRU de Nancy, Université de Lorraine, F-54000, Nancy, France

    Mikaël Agopiantz

  3. INSERM UMRS 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy, Université de Lorraine, F-54000, Nancy, France

    Mikaël Agopiantz, Shyue-Fang Battaglia-Hsu, Jean-Michel Vignaud, Abderrahim Oussalah, Guillaume Gauchotte & Hélène Busby-Venner

  4. Department of Endocrine Surgery, CHRU de Nancy, Université de Lorraine, F-54500, Vandœuvre-lès-Nancy, France

    Laurent Brunaud & Claire Nomine

  5. Department of Molecular Medicine and Personalized Therapeutics, Division of Biochemistry, Molecular Biology, Nutrition, and Metabolism, CHRU de Nancy, F-54000, Nancy, France

    Shyue-Fang Battaglia-Hsu & Abderrahim Oussalah

  6. Centre de Ressources Biologiques, BB-0033-00035, CHRU de Nancy, F-54000, Nancy, France

    Sandra Lomazzi, Jean-Michel Vignaud & Guillaume Gauchotte

  7. Department of Endocrinology, CHRU de Nancy, Université de Lorraine, F-54500, Vandœuvre-lès-Nancy, France

    Georges Weryha

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  1. Charlie Pierre
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Contributions

G.G. designed the study, developed the methodology, performed the statistical analyses, and wrote the manuscript. M.A. and H.B.-V. designed the study, developed the methodology, collected the data, and wrote the manuscript. Ch.P. collected and analyzed the data and wrote the manuscript. L.B. designed the study, developed the methodology, and collected the data. G.W. designed the study, developed the methodology, and collected the data. S.-F.B.-H. wrote and edited the manuscript. A.M., Ce.P., and C.N. collected and analyzed the data. S.L. developed the methodology and collected the data. J.-M.V. developed the methodology and edited the manuscript. A.O. performed the statistical analyses and wrote the manuscript. All authors have reviewed and approved the manuscript.

Corresponding author

Correspondence to Guillaume Gauchotte.

Ethics declarations

The experiments reported here were carried out according to the Declaration of Helsinki principles and in agreement with the French laws on biomedical research (institutional review board n°DC2008-459; CNIL declaration n°1209171).

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The authors declare that they have no conflict of interest.

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Pierre, C., Agopiantz, M., Brunaud, L. et al. COPPS, a composite score integrating pathological features, PS100 and SDHB losses, predicts the risk of metastasis and progression-free survival in pheochromocytomas/paragangliomas. Virchows Arch 474, 721–734 (2019). https://doi.org/10.1007/s00428-019-02553-5

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