Overexpression of ERBB-2 was more frequently detected in malignant than benign pheochromocytomas by multiplex ligation-dependent probe amplification and immunohistochemistry.

Abstract

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.

• Authors: WenQi Yuan, WeiQinq Wang, Bin Cui, TingWei Su, Yan Ge, Lei Jiang, WeiWei Zhou, Guang Ning
• Journal: Endocrine-related cancer (Endocr Relat Cancer) Vol. 15 Issue 1 Pg. 343-50 (Mar 2008) ISSN: 1351-0088 [Print] England
• PMID: 18310300 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adolescent
• Adrenal Gland Neoplasms (genetics, pathology)
• Adult
• Aged
• Brain Neoplasms (genetics, secondary)
• Chromosomes, Human (genetics)
• Female
• Gene Amplification
• Genes, erbB-2 (genetics)
• Genome, Human
• Humans
• Immunoenzyme Techniques
• Liver Neoplasms (genetics, secondary)
• Lung Neoplasms (genetics, secondary)
• Lymphatic Metastasis
• Male
• Middle Aged
• Paraganglioma (genetics, pathology)
• Pheochromocytoma (classification, genetics, secondary)
• Prognosis