Increased Presence of Stromal Myofibroblasts and Tenascin-C With Malignant Progression in Canine Mammary Tumors

Abstract

The aims of this study were to determine whether the appearance of stromal myofibroblasts and the expression of tenascin-C (Tn-C) correlate with the grade of malignancy in canine mammary tumors and to determine the main cellular source of Tn-C in these tumors. Single or double immunostaining using antibodies against a-smooth muscle actin (a-SMA) and Tn-C was performed on serial sections of normal canine mammary glands as well as those with lobular hyperplasia, simple adenoma, and simple carcinoma. Thirty-nine of 42 simple carcinomas (93%) exhibited stromal a-SMA-positive myofibroblasts and Tn-C expression. Only 6 of 11 cases of simple adenoma (55%) showed these changes, whereas no changes were observed in normal mammary gland tissue or cases of lobular hyperplasia. The distribution of stromal Tn-C correlated with the presence of myofibroblasts. However, Tn-C immunoreactivity was also occasionally observed in the basement membrane zone surrounding the myoepithelial layer in normal tissue, benign lesions, and tubulopapillary carcinomas. This pattern of staining was not related to the presence of myofibroblasts. The appearance of stromal myofibroblasts and expression of Tn-C were significantly correlated with higher histological grades of malignancy and vascular/lymphatic invasion in simple carcinomas. Stromal myofibroblasts appear to be a major cellular source of Tn-C and play an important role in the development of canine mammary tumors. The Tn-C expressed in the basement membrane zone of normal, hyperplastic, and neoplastic mammary tissue, which is likely produced by neighboring myoepithelial cells, may differ functionally from the Tn-C produced by myofibroblasts.

Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas

“…Importantly, we could further validate our observations by an IHC analysis of αSMA protein levels, which were significantly upregulated in stromal cells of the tumour but not in normal stroma ( Figures 3A, 4A and 5A). This finding is consistent with another report demonstrating an increase in aSMA immunoreactivity in stroma of canine simple mammary carcinomas [48]. The specific localisation of staining with αSMA to CAS but not normal stroma or neoplastic epithelial cells further underlined the specificity of our approach in isolating CAS and normal stroma by LCM.…”

Differences in Indicators of Malignancy Between Luminal Epithelial Cell Type and Myoepithelial Cell Type of Simple Solid Carcinoma in the Canine Mammary Gland

“…The higher proportion of stroma in the true SSC could possibly reflect the potential for greater infiltration, because tumor stroma is most likely related to tumor progression. 11 Our previous study indicated that the appearance of stromal myofibroblasts is associated with poor prognosis for canine mammary simple carcinoma.…”

Histologic Evidence of the "Sick Lobe" Carcinogenesis Theory and the Frequency of Intraepithelial Lesions in the Mammary Glands of Female Canines with no Clinical Signs of Neoplasia

“…3) The use of 'intraepithelial' means that these pathologies are independent of their immediate environment; however, as recent research demonstrates, the stroma has a more significant role in the evolution of these lesions than previously acknowledged [20,[46][47][48][49][50][51][52][53][54]. Our own research in canines clearly shows that these pathologies are accompanied by significant (and to some extent are dependent on) changes starting in early development not only of myoepithelial cells but also their surrounding microenvironment, which includes the basal membrane, the amount of connective tissue and the infiltration of leukocytes [19,[55][56][57][58][59][60][61][62][63][64][65][66][67].…”