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Cyclooxygenase-2 Expression in Feline Mammary Carcinomas and Adjacent Mammary Gland
62
ESVP/ECVP Proceedings 2012
148:1, 2013
HISTOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY OF CANINE MAMMARY SARCOMAS I. Dolka *, R. Sapierzy nski * and M. Kr oly *Department of Pathology and Veterinary Diagnostics and yDepartment of Physiological Sciences, Warsaw University of Life Sciences, Poland Introduction: Canine mammary sarcomas (CMS) are very rarely diagnosed and they have not yet been evaluated fully. The aim of this study was to estimate the prevalence of CMS and to characterize them by histopathology and immunohistochemistry (IHC). Materials and Methods: Paraffin wax-embedded tissue samples collected within the last 15 years were evaluated by examination of HE-stained sections. Sixteen cases were examined by IHC for expression of Vim, CK, a-SMA, Des, p63, Ki67, p53, ORa and PR. Based on the degree of differentiation, CMS were classified into low grade and high grade. Results: CMS comprised 32 (4.2%) of all canine mammary tumors (CMTS). They constituted 5.2% of all malignant CMTs. The ratio of sarcomas to carcinomas was 1:18. The most commonly diagnosed were osteosarcomas, fibrosarcomas and liposarcomas. The mean age of affected bitches was 11 years. In all CMS the expression of Vim was detected. a-SMA and Des expression was found in 37.5% and 6.3% of cases, respectively. CK, p63 and ORa expression was not observed. There was a significant correlation between the types of CMS and expression of Vim. Ki67 and p53 expression were frequently detected in high-grade CMS; however, only Ki67 showed a positive correlation. There was p53 and PR positivity (56% and 25%, respectively). Conclusions: Prospective determination of Ki67 may be useful in CMS grading. Our results expand knowledge about CMS and IHC facilitates the diagnosis of CMS.
HEPCIDIN EXPRESSION IN CANINE AND FELINE MAMMARY TUMOURS O. Marques, A. Canadas, A. R^ ema, F. Faria, J. Sim~ ao, F. G€ artner, B. Martins da Silva, G. Porto and C. Lopes Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal Introduction: Iron is an essential element involved in oxygen transport and in the activity of vital enzymes. Since it is critical for cell proliferation and given that neoplastic cells have higher requirements for iron, several authors have presented evidence linking iron with mammalian carcinogenesis. The expression of hepcidin, a key regulator of iron metabolism, was assessed in canine and feline mammary tumours. Materials and Methods: Hepcidin expression was evaluated by immunohistochemistry in 21 canine and 20 feline tissue microarray tumour samples. Normal human liver was used as a positive control. Perls’ Prussian blue staining was performed to assess haemosiderin deposits. Results: Most tumour samples showed cytoplasmic expression of hepcidin (62.5% in the dog and 90% in the cat). Additionally, luminal and nuclear immunoreactivity was also found in 62.5% and 25% of canine, and in 80% and 55% of feline samples, respectively. Perls’ positivity was observed in 80.9% of canine and in 45.4% of feline samples, mostly in inflammatory stromal cells. Tumour cells with haemosiderin deposits were also found in 47.6% of canine and 31.8% of feline tumours. Conclusions: We describe for the first time the expression of hepcidin in canine and feline mammary tumours. These results have profound implications for knowledge of the role of iron in mammalian carcinogenesis, particularly in the mammary gland.
IMMUNOHISTOCHEMICAL EXPRESSION OF MATRIX METALLOPROTEINASE 2 (MMP-2) IN FELINE FIBROADENOMATOUS CHANGE Y. Mill an *, R. De Maria y, L. Maniscalco y, S. Iussich y, R. S anchez-C espedez *, S. Guil-Luna * and J. Martın de las Mulas* *Edificio de Sanidad Animal, Campus de Rabanales, Cordoba University and y Department of Animal Pathology, University of Turin, Turin, Italy Introduction: Growth factors and hormones modulate matrix metalloproteinase (MMP)-2 expression at the intracellular and extracellular levels. Feline fibroadenomatous change (FFAC) is a non-neoplastic, progesterone-responsive condition characterized by rapid proliferation of mammary stroma and duct epithelium. The aim of this study was to analyze the tissue-specific and cell-specific distribution patterns of MMP-2 in the different cellular compartments of FFAC in comparison with PR, GH and IGF-I status. Materials and Methods: Nineteen cases of FFAC were retrieved from the archive of our institution. Immunohistochemistry was performed using the avidinebiotin peroxidase complex (ABC) method. Results: Eighty-four percent of cases expressed MMP-2 in the specialized stroma of FFAC lobules either exclusively (n 5 4) or with epithelial expression (n 5 12, P 5 0.0361). Fibroblasts (100%) and extracellular matrix (56%) were positive. Immunoreactivity was homogeneous throughout the lesion as were PR and GH reactions, found in all cases. In contrast, IGF-I was expressed in the same cases as MMP-2, but at the site of ductal budding exclusively. The simultaneous expression of MMP-2, GH and IGF-I in the stroma was seen in 42% cases. Conclusions: These results suggest that MMP-2 participates in the proliferation of the stromal compartment of FFAC together with GH and IGF-I under the influence of progesterone.
CYCLOOXYGENASE-2 EXPRESSION IN FELINE MAMMARY CARCINOMAS AND ADJACENT MAMMARY GLAND F. Seixas *, S. Silva *, M.A. Pires * and C. Lopesy *CECAV-UTAD and yICBAS-UP, Portugal Introduction: Cyclooxygenase (COX)-2 expression has been documented in many epithelial tumours in man and animals. In mammary tumours of the bitch COX-2 overexpression is associated with poor prognosis. The purpose of this study was to assess the expression of COX-2 in feline mammary carcinomas and adjacent mammary gland. Materials and Methods: We analyzed 45 primary feline mammary carcinomas and adjacent mammary gland obtained from the UTAD Pathology Laboratory. Normal mammary tissue from queens devoid of mammary tumours was used as control. COX-2 immunohistochemistry was performed by the modified avidinebiotin peroxidase complex method. Results: Non-neoplastic mammary gland adjacent to carcinomas showed moderate to strong membranous immunoreactivity, in most cases weaker than that observed in the carcinoma. Moderate to strong expression was also observed in the control gland. Most carcinomas showed moderate or strong positivity that was membranous, cytoplasmic and occasionally perinuclear in distribution. Immunoreactivity was associated with stage and invasion, but not with ulceration, histological grade, vascular invasion or metastasis. However, most high-grade and metastatic carcinomas showed strong expression. In most cases carcinoma in situ immunoreactivity was similar to that observed in invasive carcinomas. Conclusions: Non-neoplastic mammary glands consistently expressed COX-2. COX-2 internalization can be an early event in mammary tumourigenesis. Our results highlight the need for further studies to verify the real importance of COX-2 in the pathophysiology of mammary tissue.
ESVP/ECVP Proceedings 2012
148:1, 2013
HISTOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY OF CANINE MAMMARY SARCOMAS I. Dolka *, R. Sapierzy nski * and M. Kr oly *Department of Pathology and Veterinary Diagnostics and yDepartment of Physiological Sciences, Warsaw University of Life Sciences, Poland Introduction: Canine mammary sarcomas (CMS) are very rarely diagnosed and they have not yet been evaluated fully. The aim of this study was to estimate the prevalence of CMS and to characterize them by histopathology and immunohistochemistry (IHC). Materials and Methods: Paraffin wax-embedded tissue samples collected within the last 15 years were evaluated by examination of HE-stained sections. Sixteen cases were examined by IHC for expression of Vim, CK, a-SMA, Des, p63, Ki67, p53, ORa and PR. Based on the degree of differentiation, CMS were classified into low grade and high grade. Results: CMS comprised 32 (4.2%) of all canine mammary tumors (CMTS). They constituted 5.2% of all malignant CMTs. The ratio of sarcomas to carcinomas was 1:18. The most commonly diagnosed were osteosarcomas, fibrosarcomas and liposarcomas. The mean age of affected bitches was 11 years. In all CMS the expression of Vim was detected. a-SMA and Des expression was found in 37.5% and 6.3% of cases, respectively. CK, p63 and ORa expression was not observed. There was a significant correlation between the types of CMS and expression of Vim. Ki67 and p53 expression were frequently detected in high-grade CMS; however, only Ki67 showed a positive correlation. There was p53 and PR positivity (56% and 25%, respectively). Conclusions: Prospective determination of Ki67 may be useful in CMS grading. Our results expand knowledge about CMS and IHC facilitates the diagnosis of CMS.
HEPCIDIN EXPRESSION IN CANINE AND FELINE MAMMARY TUMOURS O. Marques, A. Canadas, A. R^ ema, F. Faria, J. Sim~ ao, F. G€ artner, B. Martins da Silva, G. Porto and C. Lopes Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal Introduction: Iron is an essential element involved in oxygen transport and in the activity of vital enzymes. Since it is critical for cell proliferation and given that neoplastic cells have higher requirements for iron, several authors have presented evidence linking iron with mammalian carcinogenesis. The expression of hepcidin, a key regulator of iron metabolism, was assessed in canine and feline mammary tumours. Materials and Methods: Hepcidin expression was evaluated by immunohistochemistry in 21 canine and 20 feline tissue microarray tumour samples. Normal human liver was used as a positive control. Perls’ Prussian blue staining was performed to assess haemosiderin deposits. Results: Most tumour samples showed cytoplasmic expression of hepcidin (62.5% in the dog and 90% in the cat). Additionally, luminal and nuclear immunoreactivity was also found in 62.5% and 25% of canine, and in 80% and 55% of feline samples, respectively. Perls’ positivity was observed in 80.9% of canine and in 45.4% of feline samples, mostly in inflammatory stromal cells. Tumour cells with haemosiderin deposits were also found in 47.6% of canine and 31.8% of feline tumours. Conclusions: We describe for the first time the expression of hepcidin in canine and feline mammary tumours. These results have profound implications for knowledge of the role of iron in mammalian carcinogenesis, particularly in the mammary gland.
IMMUNOHISTOCHEMICAL EXPRESSION OF MATRIX METALLOPROTEINASE 2 (MMP-2) IN FELINE FIBROADENOMATOUS CHANGE Y. Mill an *, R. De Maria y, L. Maniscalco y, S. Iussich y, R. S anchez-C espedez *, S. Guil-Luna * and J. Martın de las Mulas* *Edificio de Sanidad Animal, Campus de Rabanales, Cordoba University and y Department of Animal Pathology, University of Turin, Turin, Italy Introduction: Growth factors and hormones modulate matrix metalloproteinase (MMP)-2 expression at the intracellular and extracellular levels. Feline fibroadenomatous change (FFAC) is a non-neoplastic, progesterone-responsive condition characterized by rapid proliferation of mammary stroma and duct epithelium. The aim of this study was to analyze the tissue-specific and cell-specific distribution patterns of MMP-2 in the different cellular compartments of FFAC in comparison with PR, GH and IGF-I status. Materials and Methods: Nineteen cases of FFAC were retrieved from the archive of our institution. Immunohistochemistry was performed using the avidinebiotin peroxidase complex (ABC) method. Results: Eighty-four percent of cases expressed MMP-2 in the specialized stroma of FFAC lobules either exclusively (n 5 4) or with epithelial expression (n 5 12, P 5 0.0361). Fibroblasts (100%) and extracellular matrix (56%) were positive. Immunoreactivity was homogeneous throughout the lesion as were PR and GH reactions, found in all cases. In contrast, IGF-I was expressed in the same cases as MMP-2, but at the site of ductal budding exclusively. The simultaneous expression of MMP-2, GH and IGF-I in the stroma was seen in 42% cases. Conclusions: These results suggest that MMP-2 participates in the proliferation of the stromal compartment of FFAC together with GH and IGF-I under the influence of progesterone.
CYCLOOXYGENASE-2 EXPRESSION IN FELINE MAMMARY CARCINOMAS AND ADJACENT MAMMARY GLAND F. Seixas *, S. Silva *, M.A. Pires * and C. Lopesy *CECAV-UTAD and yICBAS-UP, Portugal Introduction: Cyclooxygenase (COX)-2 expression has been documented in many epithelial tumours in man and animals. In mammary tumours of the bitch COX-2 overexpression is associated with poor prognosis. The purpose of this study was to assess the expression of COX-2 in feline mammary carcinomas and adjacent mammary gland. Materials and Methods: We analyzed 45 primary feline mammary carcinomas and adjacent mammary gland obtained from the UTAD Pathology Laboratory. Normal mammary tissue from queens devoid of mammary tumours was used as control. COX-2 immunohistochemistry was performed by the modified avidinebiotin peroxidase complex method. Results: Non-neoplastic mammary gland adjacent to carcinomas showed moderate to strong membranous immunoreactivity, in most cases weaker than that observed in the carcinoma. Moderate to strong expression was also observed in the control gland. Most carcinomas showed moderate or strong positivity that was membranous, cytoplasmic and occasionally perinuclear in distribution. Immunoreactivity was associated with stage and invasion, but not with ulceration, histological grade, vascular invasion or metastasis. However, most high-grade and metastatic carcinomas showed strong expression. In most cases carcinoma in situ immunoreactivity was similar to that observed in invasive carcinomas. Conclusions: Non-neoplastic mammary glands consistently expressed COX-2. COX-2 internalization can be an early event in mammary tumourigenesis. Our results highlight the need for further studies to verify the real importance of COX-2 in the pathophysiology of mammary tissue.