Abstract
Mammary gland tumors are one of the most common neoplasms in female dogs, and certain breeds are prone to develop the disease. The use of biomarkers in canines is still restricted to research purposes. Therefore, the necessity to analyze gene profiles in different mammary entities in large sample sets is evident in order to evaluate the strength of potential markers serving as future prognostic factors. The aim of the present study was to analyze the gene expression of 16 target genes (BRCA1, BRCA2, FOXO3, GATA4, HER2, HMGA1, HMGA2, HMGB1, MAPK1, MAPK3, MCL1, MYC, PFDN5, PIK3CA, PTEN, and TP53) known to be involved in human and canine mammary neoplasm development. Expression was analyzed in 111 fresh frozen (FF) and in 170 formalin-fixed, paraffin-embedded (FFPE) specimens of neoplastic and non-neoplastic canine mammary tissues using a multiplexed branched-DNA (b-DNA) assay. TP53, FOXO3, PTEN, and PFDN5 expression revealed consistent results with significant low expression in malignant tumors. The possibility of utilizing them as predictive factors as well as for assisting in the choice of an adequate gene therapy may help in the development of new and improved approaches in canine mammary tumors.
Highlights
50% of canine mammary tumors appear to be malignant [1,2]
The present study proposes the concomitant analysis of 16 onco- and suppressor-genes (BRCA1, BRCA2, FOXO3, GATA4, HER2, HMGA1, HMGA2, HMGB1, MAPK1, MAPK3, MCL1, MYC, PFDN5, PIK3CA, PTEN, and TP53) regarded as being involved in neoplasm development using multiplex branched-DNA technology in fresh frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) tissues
The remaining samples of GATA4, HMGA2, and BRCA1 as well as all specimens of MYC, BRCA2, and MAPK1 in both FF and FFPE samples revealed low expression and no significant differences were found between the histologic groups
Summary
50% of canine mammary tumors appear to be malignant [1,2]. The highest relative risk ratio of developing benign mammary tumors was found in Yorkshire terriers followed by poodles, dachshunds, and cocker spaniels in Germany. The prevalence was higher in poodles followed by dachshunds, cocker spaniels, and Yorkshire terriers [4]. The postoperative median survival time can be shorter than two years depending on the clinical stage and histologic grade of the tumor [5]. The clinical stage at mammary tumor diagnosis is one of the most important prognostic factors in dogs [6]. It is only possible to be assessed in symptomatic patients and is not suitable as a mammary tumor predictive parameter
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