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.