Expression of Podoplanin in Mammary Cancers in Female Dogs

Abstract

Background/Aim: Mammary neoplasms are very common tumours in female dogs. Cancer-associated fibroblasts (CAFs) play an important role in the oncogenesis process. One of the useful proteins used in the diagnostics of CAFs cells is podoplanin (PDPN). The aim of our study was to assess the expression of PDPN in mammary cancer in female dogs. Materials and Methods: Our study cohort included 61 cancers and 21 adenomas of the mammary tumour in bitches. Expression of podoplanin, Ki-67 and HER2 was determined using the Immunohistochemical (IHC) method. PDPN expression at the mRNA level was determined using real-time PCR. Results: Expression of PDPN in CAFs was observed in 22.9% of cases of mammary cancers in bitches, with no PDPN expression in adenomas. A positive correlation was found between the expression of PDPN in CAFs and the grade of histological malignancy and expression of Ki-67. Conclusion: PDPN plays a significant role during the process of carcinogenesis of mammary tumours in female dogs. Cancer in the form of mammary tumours represents one of the most common oncological lesions in dogs (bitches). They are found mainly in the form of malignant lesions (cancers), and much less frequently in the form of benign lesions (adenomas) (1-5). In the majority of bitches, the cancer process occurs in older animals and is located in the caudal ventral and inguinal region of the mammary ridge (1-4). The most commonly used diagnostic methods are i) biopsy and ii) histopathological examination following mastectomy. The final prognosis is based on the diagnosis of the type of tumour and the degree of histological malignancy, while in doubtful cases immunohistochemical (IHC) tests are used (4, 6). Most published research focuses on assessing the type of cancer cells in order to determine the malignancy of the lesion and the prognosis for the patient (7-11). Following the trends in human medicine, more and more attention is also directed towards the analysis of the cancerous stroma, whose elements are, among others, the so-called cancer-associated fibroblasts (CAFs). CAFs are part of the stroma of many types of cancers, and their presence in breast cancer in women has been confirmed in many scientific reports (12-15). The origin of CAFs is not yet fully understood, however, it is believed that these cells may originate from local fibroblasts, modified epithelial cells, bone marrow stem cells or cells undergoing epithelial-mesenchymal transition (EMT), and, according to recent reports, from local adipocytes (16-18). It has also been reported that CAFs present in breast cancers show differences in functions as well as in gene expression compared to typical fibroblasts found in the body (13-14, 19). Moreover, CAFs in the tumour microenvironment affect the tumour development and its metastatic potential. This is due to the ability of CAFs to secrete many different cytokines, including epidermal growth factor (EGF), stromal cell-derived factor-1 (SDF-1), transforming growth factor β (TGF-β), hepatocyte growth factor (HGF), and vasc...

Expression of Periostin in Mammary Cancer Cells of Female Dogs

“…In the performed analyses, we showed a statistically positive correlation between the expression of POSTN and the expression of cell proliferation antigen Ki-67 in cancer cells in mammary cancer. The presented results are consistent with studies indicating a positive relationship between POSTN expression in cancer cells and the intensity of Ki-67 expression in breast cancer in women (38). The results of our research indicate that POSTN may be associated with the progression and increase of invasion of mammary glands in bitches.…”

“…One of the elements of the tumour stroma are cancerassociated fibroblast (CAFs) cells that play an important role in the process of carcinogenesis in humans (8,9,12). In our previous studies using IHC, podoplanin (PDPN) and POSTN expression in CAFs was found in mammary tumours in bitches (25,38). Morover POSTN expression at mRNA level was found in mammary tumours in female dogs (25,39,40).…”

Canine Mammary Cancer: State of the Art and Future Perspectives

“…In canine mammary cancer, there is an increased expression of periostin in CAFs compared to mammary adenomas, and this has a positive correlation with the histological malignancy grade [85]. Similarly, the expression of podoplanin, a protein utilized to identify CAFs, showed a positive correlation with the histological malignancy grade in canine mammary cancer [82].…”

“…Another element that participates in the process of carcinogenesis is cancer-associated fibroblasts (CAFs). These cells are part of the stroma and participate in the epithelialmesenchymal transition, secrete cytokines such as epidermal growth factor and transforming growth factor β and produce metalloproteinases that promote growth and tumor progression, invasiveness and metastasis [82][83][84]. In canine mammary cancer, there is an increased expression of periostin in CAFs compared to mammary adenomas, and this has a positive correlation with the histological malignancy grade [85].…”