PMID- 26749044 OWN - NLM STAT- MEDLINE DCOM- 20170502 LR - 20181017 IS - 1365-2265 (Electronic) IS - 0300-0664 (Linking) VI - 84 IP - 6 DP - 2016 Jun TI - ERBB-2 overexpression as a risk factor for malignant phaeochromocytomas and paraganglinomas. PG - 822-9 LID - 10.1111/cen.13019 [doi] AB - OBJECTIVE: There are currently no good histological or molecular markers to differentiate benign from malignant phaeochromocytomas and paraganglinomas (PPGLs). Our previous cross-sectional study observed that ERBB-2 overexpression was associated with malignant PPGLs. This study aimed to evaluate the predictive value of ERBB-2 overexpression for metastasis in PPGLs in a large population. METHODS: A total of 262 patients diagnosed as PPGLs in our institution between 2002 and 2012 were included. We analysed ERBB-2 protein expression in the primary PPGL tumours by immunohistochemistry (IHC) and ERBB-2 amplification by fluorescence in situ hybridization (FISH). Direct Sanger sequencing was performed to examine ERBB-2 exon 20 mutations. The occurrence of malignant PPGLs was documented in the follow-up period. Kaplan-Meier analysis and Cox proportional hazard models were used to evaluate the association between ERBB-2 overexpression and metastasis of PPGLs. RESULTS: Twenty-six (9.9%) patients had ERBB-2 overexpression in their primary PPGL tumours, which was significantly associated with ERBB-2 amplification (17/25, 68%). No ERBB-2 mutation was found. At a median follow-up of 4.5 years, a total of 23 malignant PPGLs were documented, including eight (30.8%) patients in the ERBB-2 overexpression group and 15 (6.4%) patients in the ERBB-2-negative group. The incidence rate of metastasis was 5.3 per 100 person-years vs 1.4 per 100 person-years in the ERBB-2 overexpression and ERBB-2-negative groups (P < 0.001), respectively. Kaplan-Meier analysis showed that ERBB-2 overexpression was associated with decreased metastasis-free survival (P = 0.001, log-rank test). After adjusting for primary tumour size and location, Cox regression analysis revealed that ERBB-2 overexpression was independently associated with risk of malignant PPGLs (HR = 2.78; 95% CI, 1.12-6.90; P = 0.028). CONCLUSION: Patients harbouring tumours with ERBB-2 overexpression have a significantly higher risk of developing malignant PPGLs. CI - (c) 2016 John Wiley & Sons Ltd. FAU - Wang, Weiqing AU - Wang W AD - Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. AD - Laboratory for Endocrine & Metabolic Diseases of Institute of Health Science, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 227 South ChongQing Road, Shanghai, China. FAU - Zhong, Xu AU - Zhong X AD - Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. FAU - Ye, Lei AU - Ye L AD - Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. AD - Laboratory for Endocrine & Metabolic Diseases of Institute of Health Science, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 227 South ChongQing Road, Shanghai, China. FAU - Qi, Yan AU - Qi Y AD - Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. FAU - Su, TingWei AU - Su T AD - Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. FAU - Wei, Qing AU - Wei Q AD - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, China. FAU - Xie, Jing AU - Xie J AD - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, China. FAU - Jiang, Lei AU - Jiang L AD - Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. FAU - Jiang, Yiran AU - Jiang Y AD - Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. FAU - Zhou, Weiwei AU - Zhou W AD - Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. FAU - Cui, Bin AU - Cui B AD - Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. AD - Laboratory for Endocrine & Metabolic Diseases of Institute of Health Science, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 227 South ChongQing Road, Shanghai, China. FAU - Ning, Guang AU - Ning G AD - Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. AD - Laboratory for Endocrine & Metabolic Diseases of Institute of Health Science, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 227 South ChongQing Road, Shanghai, China. LA - eng SI - GENBANK/NM_001289937 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160225 PL - England TA - Clin Endocrinol (Oxf) JT - Clinical endocrinology JID - 0346653 RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adrenal Gland Neoplasms/diagnosis/pathology MH - Adult MH - Diagnosis, Differential MH - Female MH - Gene Amplification MH - Genes, erbB-2/genetics MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Mutation MH - Neoplasm Metastasis/genetics MH - Paraganglioma/*diagnosis/pathology MH - Pheochromocytoma/*diagnosis/pathology MH - Receptor, ErbB-2/*analysis/genetics MH - Risk Factors EDAT- 2016/01/11 06:00 MHDA- 2017/05/04 06:00 CRDT- 2016/01/11 06:00 PHST- 2015/08/05 00:00 [received] PHST- 2015/09/25 00:00 [revised] PHST- 2015/11/22 00:00 [revised] PHST- 2015/12/21 00:00 [accepted] PHST- 2016/01/11 06:00 [entrez] PHST- 2016/01/11 06:00 [pubmed] PHST- 2017/05/04 06:00 [medline] AID - 10.1111/cen.13019 [doi] PST - ppublish SO - Clin Endocrinol (Oxf). 2016 Jun;84(6):822-9. doi: 10.1111/cen.13019. Epub 2016 Feb 25.