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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.

Yuan W, Wang W, Cui B, Su T, Ge Y, Jiang L, Zhou W, Ning G - Endocr. Relat. Cancer (2008)

Bottom Line: There is no significant difference among the three groups of pheochromocytomas.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrine and Metabolic Diseases, School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai JiaoTong University, Shanghai, PR China.

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.

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Strong positive staining (+++) of the malignant pheochromocytoma (top left),++ of the paraganglioma (top right),+ of the benign pheochromocytoma (bottom left), and negative control (bottom right). Magnification, ×40.
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fig2: Strong positive staining (+++) of the malignant pheochromocytoma (top left),++ of the paraganglioma (top right),+ of the benign pheochromocytoma (bottom left), and negative control (bottom right). Magnification, ×40.

Mentions: To study the expression of ERBB-2 oncogene in pheochromocytomas, we further analyzed 39 out of the 43 samples by IHC analysis. Positive ERBB-2 immunoreactivity showed a diffuse intra-cytoplasmic granular staining. The frequency of cells expressing the ERBB-2 protein differed among tumors. All the malignant pheochromocytoma samples showed positive ERBB-2 immunoreactivity, among them 86% were ++ or +++. None of the benign tumors showed +++, and 52% of the benign tumors showed negative immunoreactivity. No immunostaining was observed in the negative controls (Fig. 2). The Kruskal–Wallis test showed significantly higher ERBB-2 oncoprotein expression in the malignant pheochromocytomas (P=0.0065, K–W test; Table 3).


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

Yuan W, Wang W, Cui B, Su T, Ge Y, Jiang L, Zhou W, Ning G - Endocr. Relat. Cancer (2008)

Strong positive staining (+++) of the malignant pheochromocytoma (top left),++ of the paraganglioma (top right),+ of the benign pheochromocytoma (bottom left), and negative control (bottom right). Magnification, ×40.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2254511&req=5

fig2: Strong positive staining (+++) of the malignant pheochromocytoma (top left),++ of the paraganglioma (top right),+ of the benign pheochromocytoma (bottom left), and negative control (bottom right). Magnification, ×40.
Mentions: To study the expression of ERBB-2 oncogene in pheochromocytomas, we further analyzed 39 out of the 43 samples by IHC analysis. Positive ERBB-2 immunoreactivity showed a diffuse intra-cytoplasmic granular staining. The frequency of cells expressing the ERBB-2 protein differed among tumors. All the malignant pheochromocytoma samples showed positive ERBB-2 immunoreactivity, among them 86% were ++ or +++. None of the benign tumors showed +++, and 52% of the benign tumors showed negative immunoreactivity. No immunostaining was observed in the negative controls (Fig. 2). The Kruskal–Wallis test showed significantly higher ERBB-2 oncoprotein expression in the malignant pheochromocytomas (P=0.0065, K–W test; Table 3).

Bottom Line: There is no significant difference among the three groups of pheochromocytomas.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrine and Metabolic Diseases, School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai JiaoTong University, Shanghai, PR China.

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.

Show MeSH
Related in: MedlinePlus