Abstract
The incidence and prevalence of paraneoplastic glomerulopathy, especially associated with carcinoma, are a matter of debate and the causal link between cancer and glomerular diseases remains unclear. The aim of this study was to evaluate renal biopsies of selected bitches with spontaneous mammary gland carcinoma. We hypothesized that dogs with mammary carcinomas would show histologic evidence of glomerular pathology. A prospective study was performed in dogs with naturally occurring mammary carcinoma that were undergoing tumor resection and ovariohysterectomy. We evaluated renal biopsies of 32 bitches with spontaneous mammary gland carcinoma and 11 control dogs without mammary gland neoplasia. Samples were obtained from the left kidney and the biopsy material was divided for light microscopy (LM), immunofluorescence (IF) and transmission electron microscopy (TEM). Light microscopy abnormalities were identified in 78.1% of dogs with mammary carcinoma (n = 25) and in none of the dogs in the control group. Focal glomerular mesangial matrix expansion was the most common alteration (n = 15, 60.0%), but mesangial cell proliferation (n = 9, 36.0%) and focal segmental glomerulosclerosis (n = 9, 36.0%), synechiae (n = 7, 28.0%), and globally sclerotic glomeruli (n = 6, 24.0%) were also frequent in dogs with malignancy. Immunofluorescence microscopy revealed strong IgM staining was demonstrated in 64.3% (n = 18) of carcinoma dogs. Transmission electron microscopy from dogs with carcinoma revealed slight changes, the most frequent of which was faint sub-endothelial and mesangial deposits of electron-dense material (78%). Mesangial cell interpositioning and segmental effacement of podocyte foot processes were identified in some specimens (45%). Changes in the glomerulus and proteinuria are common in dogs with naturally occurring mammary carcinoma and this condition appears to provide an excellent large animal model for cancer-associated glomerulopathy in humans.
Highlights
Breast cancer is considered one of the most common malignancies affecting humans and is an area of intense research [1]
The results of our current study provides strong evidence that dogs with naturally occurring mammary carcinoma have an increased risk for development of subclinical proteinuria and glomerular lesions, similar to those described in humans with early stage neoplasms and subclinical glomerular disease [17]
Mammary carcinoma in dogs was associated with increased urine protein/creatinine ratio (UPC) and approximately one-third of the dogs in the carcinoma group were proteinuric (UPC>0.5)
Summary
Breast cancer is considered one of the most common malignancies affecting humans and is an area of intense research [1]. Occurring mammary carcinoma is seen with a high incidence in bitches, and dogs might serve as an excellent model for human disease [2]. While much information has been gathered about the biological behavior of breast cancer, the pathophysiology of solid tumor-associated glomerulopathies remains obscure [3,4,5]. Glomerular pathology associated with malignancy is not uncommon in human patients [6] and affected patients have been reported to develop renal failure, paraneoplastic glomerulopathy and sometimes nephrotic syndrome [7]. The rodent model of carcinoma is poorly correlated with the human model because rats often die before developing proteinuria [3]
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