RESEARCH ARTICLE
Validation of pathological grading systems for predicting metastatic potential in pheochromocytoma and paraganglioma Jung-Min Koh1, Seong Hee Ahn2, Hyeonmok Kim3, Beom-Jun Kim1, Tae-Yon Sung4, Young Hoon Kim4, Suck Joon Hong4, Dong Eun Song5‡*, Seung Hun Lee1‡*
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1 Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, 2 Department of Endocrinology, Inha University School of Medicine, Incheon, Korea, 3 Division of Endocrinology and Metabolism, Department of Medicine, Gyeongsang National University School of Medicine, Jinju, Korea, 4 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, 5 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea ‡ Joint senior authors *
[email protected] (DES);
[email protected] (SHL)
Abstract OPEN ACCESS Citation: Koh J-M, Ahn SH, Kim H, Kim B-J, Sung T-Y, Kim YH, et al. (2017) Validation of pathological grading systems for predicting metastatic potential in pheochromocytoma and paraganglioma. PLoS ONE 12(11): e0187398. https://doi.org/10.1371/ journal.pone.0187398 Editor: Ales Vicha, 2nd medical school of Charles University, CZECH REPUBLIC Received: June 30, 2017 Accepted: September 26, 2017
Purpose The Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) was proposed for predicting the metastatic potential of pheochromocytoma and paraganglioma to overcome the limitations of the Pheochromocytoma of the Adrenal Scaled Score (PASS). However, to date, no study validating the GAPP has been conducted, and previous studies did not include mutations in the succinate dehydrogenase type B (SDHB) gene in the score calculation. In this retrospective cohort study, we validated the prediction ability of GAPP and assessed whether it would be improved by inclusion of the loss of SDHB immunohistochemical staining.
Published: November 8, 2017 Copyright: © 2017 Koh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Although all participants provided written informed consents for this study, some participants did not agree to secondary use of their individual data. Therefore, we have included the participant-level data of those who did not object to secondary data use (N = 37) as a supporting information file. Additional data may be partially provided upon contacting the corresponding author of this manuscript. Funding: This study was supported by grants from the Asan Institute for Life Sciences, Seoul,
Methods We divided the tumors into non-metastatic and metastatic groups based on the presence of synchronous or metachronous metastases. The GAPP score and PASS at the initial operation were measured. Moreover, we combined some GAPP parameters with the immunohistochemical staining of SDHB to obtain a modified GAPP (M-GAPP) score.
Results Metastasis occurred in 15/72 (20.8%) patients, with a mean follow-up of 43.5 months. Loss of SDHB staining was more frequent (P = 0.044) in the metastatic group. The GAPP score (P = 0.006), PASS (P = 0.003), and M-GAPP score (P
