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Endocrine-Related Cancer 15 (1) 343 -350     DOI: 10.1677/ERC-07-0188
Copyright © 2008 by the Society for Endocrinology
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Overexpression of ERBB-2 was more frequently detected in malignant than benign pheochromocytomas by multiplex ligation-dependent probe amplification and immunohistochemistry

WenQi Yuan1,2,, WeiQinq Wang1,3,, Bin Cui1,2, TingWei Su1, Yan Ge1,2, Lei Jiang1, WeiWei Zhou1 and Guang Ning1,2,3

1 Department of Endocrine and Metabolic Diseases, School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai JiaoTong University, 197 Ruijin Er Lu, Shanghai 200025, People's Republic of China2 Laboratory of Endocrine and Metabolic Diseases, Shanghai JiaoTong University School of Medicine and Shanghai Institutes for Biological Sciences, Institute of Health Sciences, Chinese Academy of Sciences, Shanghai 200025, China3 Division of Endocrine and Metabolic Diseases, Shanghai JiaoTong University School of Medicine, E-Institute of Shanghai Universities, Ruijin Hospital, Shanghai 200025, China

(Correspondence should be addressed to G Ning; Email: guangning{at}medmail.com.cn)

To analyze the genetic alterations of pheochromocytomas and evaluate the difference among malignant, extra-adrenal, and benign pheochromocytomas. Forty-three tumor samples were tested for genetic changes using multiplex ligation-dependent probe amplification. Among them, 39 samples were available for protein expression analysis by immunohistochemistry (IHC). All 43 patients (24 women and 19 men; mean age 44.6±13.6 years; range 18–75 years; 9 with malignant, 7 extra-adrenal, and 27 benign) showed multiple copy number losses or gains. The average copy number change was 13.10 in malignant, 13.93 in benign, and 13.47 in paraganglioma patients. There is no significant difference among the three groups of pheochromocytomas. However, we discovered that in the malignant pheochromocytomas, 6 of the 9 patients (67%) showed erythroblastic leukemia viral oncogene homolog 2 (ERBB-2) oncogene gain, whereas only 12 of the 34 (35%) identified change in the benign and extra-adrenal pheochromocytomas. Further, IHC confirmed that ERBB-2-positive staining was more frequent and stronger in malignant pheochromocytomas than in benign and extra-adrenal pheochromocytomas. Our study illustrates the chromosomal changes of the whole genome of Chinese pheochromocytoma patients. The results suggest that there may be certain progression of genetic events that involves chromosomes 1p, 3p, 6p, 11q, 12q, 17q, and 19q in the development of pheochromocytomas, and the activation of ERBB-2 located on chromosome 17q is an important and early event in the malignancy development of these tumor types. The overexpression of ERBB-2 identified by IHC suggested that this oncogene could be associated with the malignancy of pheochromocytomas and paragangliomas.







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