Abstract
The objective of the present investigation was to study the expression of c-erbB-2 and MIB-1 and try to associate them with morphological features of the cell such as nuclear pleomorphism, mitotic count and histological grade in a series of 70 canine mammary gland tumors, 22 of them benign and 48 malignant. Tumors were collected at the Veterinary Hospital of UFMG (Brazil) and the Veterinary Faculty of Porto University (Portugal). c-erbB-2 expression was determined according to the guidelines provided by the manufacturer of the HercepTest system and nuclear pleomorphism, mitotic count and histological grade according the Elston and Ellis grading system. The HercepTest is the FDA-approved in vitro diagnostic test marketed by Dako. It is a semi-quantitative immunohistochemical assay used to determine overexpression of HER2 protein (human epidermal growth factor receptor) in breast cancer tissue. MIB-1 expression was also evaluated in 28 malignant tumors. Seventeen (35.4%) of the malignant tumors were positive for c-erbB-2 expression, which was positively associated with nuclear pleomorphism (P < 0.0001), histological grade (P = 0.0017) and mitotic count (P < 0.05). Nuclear pleomorphism also showed a positive association with MIB-1 index (P < 0.0001). These results suggest that some of the biological and morphological characteristics of the tumor are associated in canine mammary gland tumors, as also reported for human breast cancer. It was also possible to show that the immunoexpression of c-erbB-2 can be a factor in mammary carcinogenesis. This fact opens the possibility of using anti-c-erbB-2 antibodies in the treatment of canine mammary tumors.
Highlights
A number of proto-oncogenes and oncogenes have been investigated in breast cancer due to their relevant roles in breast carcinogenesis, as well as for their prognostic value.Proto-oncogenes are normal genes that are usually responsible for the regulation of cell proliferation, but in mutated form promote neoplastic transformation. c-erbB-2, c-MYC, c-RAS, and RR1 are examples of some oncogenes involved in mammary carcinogenesis.The proto-oncogene c-erbB-2 is located on chromosome 17 and encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity, which has sequence homology with the epidermal growth factor receptor [1]
Tumors were collected at the Veterinary Hospital of UFMG (Brazil) and the Veterinary Faculty of Porto University (Portugal). c-erbB-2 expression was determined according to the guidelines provided by the manufacturer of the HercepTest system and nuclear pleomorphism, mitotic count and histological grade according the Elston and Ellis grading system
Seventeen (35.4%) of the malignant tumors were positive for c-erbB-2 expression, which was positively associated with nuclear pleomorphism (P < 0.0001), histological grade (P = 0.0017) and mitotic count (P < 0.05)
Summary
A number of proto-oncogenes and oncogenes have been investigated in breast cancer due to their relevant roles in breast carcinogenesis, as well as for their prognostic value.Proto-oncogenes are normal genes that are usually responsible for the regulation of cell proliferation, but in mutated form promote neoplastic transformation. c-erbB-2, c-MYC, c-RAS, and RR1 are examples of some oncogenes involved in mammary carcinogenesis.The proto-oncogene c-erbB-2 is located on chromosome 17 and encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity, which has sequence homology with the epidermal growth factor receptor [1]. Since the initial report by Slamon et al [2], which showed an association between the amplification of this gene and poor prognosis in breast cancer, several other studies have been conducted, and c-erbB-2 overexpression was detected in about 10 to 20% of invasive breast carcinomas. It is not clear, whether this overexpression is significantly associated with overall decrease survival and disease-free survival. The demonstration of a high frequency of c-erbB-2 overexpression in in situ ductal carcinomas of the breast suggests that it could be an early event in breast carcinogenesis in humans [3,4,5,6,7,8]; c-erbB-2 overexpression has been detected in dog mammary tumors [9,10]
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