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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.

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.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Yuan W,Wang W,Cui B,Su T,Ge Y,Jiang L,Zhou W,Ning G

doi

10.1677/ERC-07-0188

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

343-50

issue

eissn

1351-0088

issn

1479-6821

pii

15/1/343

journal_volume

pub_type

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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.