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Podoplanin Expression in Cancer-Associated Fibroblasts in Mammary Gland Cancer in Dogs
J. Comp. Path. 2017, Vol. 156, 54e141
ESVP and ECVP Proceedings 2016
PODOPLANIN EXPRESSION IN CANCER-ASSOCIATED FIBROBLASTS IN MAMMARY GLAND CANCER IN DOGS P. Borecka *, R. Ciaputa *, J.A. Madej *, I. Janus *, M. Kandefer-Gola *, S. Dzimira *, A. Piotrowska y, P. Dzie˛giel y and M. Nowak* *Division of Pathomorphology and Veterinary Forensics, Department of Pathology, Wroclaw University of Environmental and Life Sciences, Wroclaw and yDepartment of Histology and Embryology, Medical University of Wroclaw, Wroclaw, Poland Introduction: Mammary gland cancers are one of the most common malignant tumours in bitches. Although in veterinary medicine there are many cell markers that are useful in the diagnosis of these neoplasms, the expression of podoplanin has not been well described. This protein is a specific marker of lymphangiogenesis and is present in lymphatic endothelial cells. Moreover, expression of podoplanin was observed in cancer-associated fibroblasts (CAFs) in invasive ductal breast carcinoma in women. In women, the presence of CAFs shows a positive correlation with negative prognostic factors. Materials and Methods: The study was carried out on 55 samples of canine mammary gland cancer collected from bitches of various breeds and age. Tissue samples were fixed in 7% neutral buffered formalin, processed routinely and embedded in paraffin wax blocks. Sections were stained with haematoxylin and eosin to confirm the diagnosis (according to Goldschmidt’s classification) and to assess the histological malignancy grade. The immunohistochemical examination of the expression of podoplanin and Ki67 was made using mouse monoclonal antibodies (DAKO, Denmark). The results were subjected to statistical analysis. Results: CAF podoplanin expression was noted in 14.5% of cases. The presence of CAFs showed a positive correlation with the dogs’ age and histological malignancy grade. Moreover, in specimens with the presence of CAFs a higher proliferative potential (high expression of Ki67) was observed. Conclusions: The results suggest a role of CAFs in the progression of mammary gland neoplasms in bitches, similar to ductal breast carcinoma in women.
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IMMUNOHISTOCHEMICAL EVALUATION OF P62 IN CANINE MAMMARY TUMOURS F. Mariotti, S. Mari and G.E. Magi School of Bioscience and Veterinary Medicine, University of Camerino, Italy Introduction: P62 is a ubiquitin-binding scaffold protein considered the crossroad molecule of autophagy and apoptosis. In veterinary medicine, the role of p62 in tumours is poorly understood. The aim of this study was to evaluate the immunohistochemical expression of p62 in normal mammary tissue, in adenomas and carcinomas of the dog. Materials and Methods: The immunohistochemical analyses were performed on 36 mammary tumours classified according to WHO criteria and eight normal mammary tissues. Regional lymph nodes were analyzed when present. Results: All normal tissues exhibited a strong, homogeneous positivity. Almost all epithelial cells showed brown granular labelling in the cytoplasm, while the nucleus was negative. Only 5% of myoepithelial cells were labelled and the stroma was always negative. In all adenomas, p62 labelling was intense, but the percentage of positivelylabelled epithelial cells was lower (65%). In malignant tumours, the immunoreaction appeared heterogeneous both between samples and within the same sample. Nineteen carcinomas (68%) showed small areas of strong positive labelling adjacent to others that were weakly positive, while nine (32%) exhibited diffuse weak labelling. Metastatic cells in lymph nodes were p62 positive in 50% of cases. Conclusions: These data suggest a negative correlation between p62 expression and neoplastic progression. To date, because of the few cases examined and the complex role of p62 in autophagy and apoptosis, we believe that is not possible to consider p62 as a progression marker in mammary oncogenesis. In the future it will be interesting to compare these results with data obtained from human breast cancer studies.
ESVP and ECVP Proceedings 2016
PODOPLANIN EXPRESSION IN CANCER-ASSOCIATED FIBROBLASTS IN MAMMARY GLAND CANCER IN DOGS P. Borecka *, R. Ciaputa *, J.A. Madej *, I. Janus *, M. Kandefer-Gola *, S. Dzimira *, A. Piotrowska y, P. Dzie˛giel y and M. Nowak* *Division of Pathomorphology and Veterinary Forensics, Department of Pathology, Wroclaw University of Environmental and Life Sciences, Wroclaw and yDepartment of Histology and Embryology, Medical University of Wroclaw, Wroclaw, Poland Introduction: Mammary gland cancers are one of the most common malignant tumours in bitches. Although in veterinary medicine there are many cell markers that are useful in the diagnosis of these neoplasms, the expression of podoplanin has not been well described. This protein is a specific marker of lymphangiogenesis and is present in lymphatic endothelial cells. Moreover, expression of podoplanin was observed in cancer-associated fibroblasts (CAFs) in invasive ductal breast carcinoma in women. In women, the presence of CAFs shows a positive correlation with negative prognostic factors. Materials and Methods: The study was carried out on 55 samples of canine mammary gland cancer collected from bitches of various breeds and age. Tissue samples were fixed in 7% neutral buffered formalin, processed routinely and embedded in paraffin wax blocks. Sections were stained with haematoxylin and eosin to confirm the diagnosis (according to Goldschmidt’s classification) and to assess the histological malignancy grade. The immunohistochemical examination of the expression of podoplanin and Ki67 was made using mouse monoclonal antibodies (DAKO, Denmark). The results were subjected to statistical analysis. Results: CAF podoplanin expression was noted in 14.5% of cases. The presence of CAFs showed a positive correlation with the dogs’ age and histological malignancy grade. Moreover, in specimens with the presence of CAFs a higher proliferative potential (high expression of Ki67) was observed. Conclusions: The results suggest a role of CAFs in the progression of mammary gland neoplasms in bitches, similar to ductal breast carcinoma in women.
121
IMMUNOHISTOCHEMICAL EVALUATION OF P62 IN CANINE MAMMARY TUMOURS F. Mariotti, S. Mari and G.E. Magi School of Bioscience and Veterinary Medicine, University of Camerino, Italy Introduction: P62 is a ubiquitin-binding scaffold protein considered the crossroad molecule of autophagy and apoptosis. In veterinary medicine, the role of p62 in tumours is poorly understood. The aim of this study was to evaluate the immunohistochemical expression of p62 in normal mammary tissue, in adenomas and carcinomas of the dog. Materials and Methods: The immunohistochemical analyses were performed on 36 mammary tumours classified according to WHO criteria and eight normal mammary tissues. Regional lymph nodes were analyzed when present. Results: All normal tissues exhibited a strong, homogeneous positivity. Almost all epithelial cells showed brown granular labelling in the cytoplasm, while the nucleus was negative. Only 5% of myoepithelial cells were labelled and the stroma was always negative. In all adenomas, p62 labelling was intense, but the percentage of positivelylabelled epithelial cells was lower (65%). In malignant tumours, the immunoreaction appeared heterogeneous both between samples and within the same sample. Nineteen carcinomas (68%) showed small areas of strong positive labelling adjacent to others that were weakly positive, while nine (32%) exhibited diffuse weak labelling. Metastatic cells in lymph nodes were p62 positive in 50% of cases. Conclusions: These data suggest a negative correlation between p62 expression and neoplastic progression. To date, because of the few cases examined and the complex role of p62 in autophagy and apoptosis, we believe that is not possible to consider p62 as a progression marker in mammary oncogenesis. In the future it will be interesting to compare these results with data obtained from human breast cancer studies.