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Virchows Arch. 2019 Mar 13. doi: 10.1007/s00428-019-02553-5. [Epub ahead of print]

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

Author information

1
Department of Pathology, CHRU de Nancy, Université de Lorraine, F-54000, Nancy, France.
2
Department of Medical Gynecology, CHRU de Nancy, Université de Lorraine, F-54000, Nancy, France.
3
INSERM UMRS 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy, Université de Lorraine, F-54000, Nancy, France.
4
Department of Endocrine Surgery, CHRU de Nancy, Université de Lorraine, F-54500, Vandœuvre-lès-Nancy, France.
5
Department of Molecular Medicine and Personalized Therapeutics, Division of Biochemistry, Molecular Biology, Nutrition, and Metabolism, CHRU de Nancy, F-54000, Nancy, France.
6
Centre de Ressources Biologiques, BB-0033-00035, CHRU de Nancy, F-54000, Nancy, France.
7
Department of Endocrinology, CHRU de Nancy, Université de Lorraine, F-54500, Vandœuvre-lès-Nancy, France.
8
Department of Pathology, CHRU de Nancy, Université de Lorraine, F-54000, Nancy, France. g.gauchotte@chru-nancy.fr.
9
INSERM UMRS 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy, Université de Lorraine, F-54000, Nancy, France. g.gauchotte@chru-nancy.fr.
10
Centre de Ressources Biologiques, BB-0033-00035, CHRU de Nancy, F-54000, Nancy, France. g.gauchotte@chru-nancy.fr.

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:

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

PMID:
30868297
DOI:
10.1007/s00428-019-02553-5

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