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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

  • Charlie Pierre
  • Mikaël Agopiantz
  • Laurent Brunaud
  • Shyue-Fang Battaglia-Hsu
  • Antoine Max
  • Celso Pouget
  • Claire Nomine
  • Sandra Lomazzi
  • Jean-Michel Vignaud
  • Georges Weryha
  • Abderrahim Oussalah
  • Guillaume GauchotteEmail author
  • Hélène Busby-Venner
Original Article
  • 38 Downloads

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.

Keywords

Pheochromocytoma Paraganglioma Prognosis Metastasis MCM6 PS100 Ki-67 SDHB PASS COPPS 

Notes

Acknowledgements

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

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.

Compliance with ethical standards

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).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

428_2019_2553_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 14.9 kb)
428_2019_2553_MOESM2_ESM.docx (13 kb)
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428_2019_2553_MOESM3_ESM.docx (14 kb)
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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Charlie Pierre
    • 1
  • Mikaël Agopiantz
    • 2
    • 3
  • Laurent Brunaud
    • 4
  • Shyue-Fang Battaglia-Hsu
    • 3
    • 5
  • Antoine Max
    • 1
  • Celso Pouget
    • 1
  • Claire Nomine
    • 4
  • Sandra Lomazzi
    • 6
  • Jean-Michel Vignaud
    • 1
    • 3
    • 6
  • Georges Weryha
    • 7
  • Abderrahim Oussalah
    • 3
    • 5
  • Guillaume Gauchotte
    • 1
    • 3
    • 6
    Email author
  • Hélène Busby-Venner
    • 1
    • 3
  1. 1.Department of Pathology, CHRU de NancyUniversité de LorraineNancyFrance
  2. 2.Department of Medical Gynecology, CHRU de NancyUniversité de LorraineNancyFrance
  3. 3.INSERM UMRS 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of NancyUniversité de LorraineNancyFrance
  4. 4.Department of Endocrine Surgery, CHRU de NancyUniversité de LorraineVandœuvre-lès-NancyFrance
  5. 5.Department of Molecular Medicine and Personalized Therapeutics, Division of Biochemistry, Molecular Biology, Nutrition, and MetabolismCHRU de NancyNancyFrance
  6. 6.Centre de Ressources Biologiques, BB-0033-00035CHRU de NancyNancyFrance
  7. 7.Department of Endocrinology, CHRU de NancyUniversité de LorraineVandœuvre-lès-NancyFrance

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