Introduction

Carcinogenesis in canine mammary gland is thought to involve a series of genetic alterations in epithelial duct cells. Epithelial mammary hyperplasia is recognized as a risk factor for invasive cancer (Page 1990, Marinelli 2004). Several biological markers are altered according to the phase of mammary carcinogenesis, including adhesion molecule (E-cadherin) and proliferation markers (Ki-67). Some markers have recently been quantified in premalignant lesions as well as in invasive breast cancer (Mareel 2003, Antuofermo 2007). This study compared E-cadherin and Ki-67 immunohistochemical expression in normal, hyperplastic and neoplastic canine mammary glands.

Methods

A total of 14 mammary lesions were classified and histologic sections of the excisional specimens were evaluated for presence of usual ductal hyperplasia and atypical ductal hyperplasia. Formalin-fixed, paraffin embedded sections of mammary biopsy specimens of all cases were studied by immunohistochemical analysis with antibodies against E cadherin (clone 4A2C7; Zymed; dilution: 1:100) and Ki-67 (clone Mib-1; Dako; dilution: 1:25). The distribution of E-cadherin was evaluated semi-quantitatively and scored into five categories: from negative (-) to diffusely positive (++++) (Simpson et al. 2005). For Ki-67 staining, 500 cells from each lesion within each specimen were scored as positive or negative nuclear immunoreactivity. Staining patterns were compared between groups of lesions.

Discussion

E-cadherin was diffusely positive in normal epithelial duct cells but reduced in ductal hyperplasia and mammary neoplasias (especially in malignant tumors) (p < 0.05). The difference of immuno-expression between normal gland tissue and epithelial lesions was strengthened by presence of atypical ductal hyperplasia. The proliferative activity as measured by Ki67 appears higher in neoplastic and hyperplastic epithelial cells than in normal mammary gland.

Discussion and Conclusions

Our findings support the hypothesis that hyperplasic lesions are associated with mammary neoplasms alterations and suggest that these lesions have direct evolutionary links to malignant mammary tumors. These alterations in dogs can suggest that this specie can be used as a model in comparative studies of noninvasive breast lesions and its progression to breast cancer.

References

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