- Email: [email protected]
Expression of the Pluripotency Factor OCT4 in Cutaneous Mast Cell Tumours
114
ESVP, ECVP and NSVP Proceedings 2015
EXPRESSION OF THE PLURIPOTENCY FACTOR OCT4 IN CUTANEOUS MAST CELL TUMOURS T.H.M. Vargas *, L.H. Pulz *, C.N. Barra *, K.G. Cadrobbi *, G.C. Huete *, A.T. Nishiya y, S.R. Kleeb z, J.G. Xavier z and R.F. Strefezzi* *Laboratorio de Oncologia Comparada e Translacional, Universidade de S~ao Paulo, yUniversidade Anhembi-Morumbi and zUniversidade Metodista de S~ao Paulo, Brazil Introduction: Mast cell tumours (MCTs) comprise about 20% of the neoplasms affecting the skin of dogs, and are considered one of the major therapeutic challenges by veterinary oncologists. OCT4 is related to self-renewal and its expression can be detected in normal stem cells as well as in cancer. Cancer stem cells are believed to initiate and maintain the neoplastic cell population. These ‘tumour initiating cells’ are also associated with malignancy and resistance to chemotherapy. The aims of the present work were to investigate the immunoexpression of OCT4 in canine cutaneous MCTs and evaluate associations with histopathological grades, mortality and postsurgical survival. Materials and Methods: Twenty-eight cases of canine cutaneous MCTs were selected. The dogs were treated surgically and did not receive any adjuvant therapy. OCT4 expression was characterized by immunohistochemistry using an anti-OCT4 primary antibody (Santa Cruz Biotechnology, SC-5279). For statistical analysis, only nuclear labelling was considered positive. Results: Thirteen cases showed nuclear and cytoplasmic positivity and eight cases showed cytoplasmic labelling with few scattered positive nuclei. Cytoplasmic labelling was observed in another six MCTs and one case was negative for OCT4. OCT4 expression was not associated with the histopathological grading systems for MCTs, diseaserelated mortality or post-surgical survival. Conclusions: There are different patterns of OCT4 expression in MCTs and nuclear positivity is not an independent marker for this neoplasm. In order to confirm these observations, further studies are needed to evaluate the expression of specific isoforms of the protein.
J. Comp. Path. 2016, Vol. 154, 58e123
AN IMMUNOHISTOCHEMICAL STUDY OF EPITHELIALeMESENCHYMAL TRANSITION IN FELINE MAMMARY TUMOURS N. Karabolovski *, A. Gudan Kurilj y, K. Severin z, y staric-Zuckermann y, L. Medven y, M. Hohsteter , I.-C. So Grabarevicy B. Artukovic y and Z. *Department of Veterinary Pathology, University St. Climent Ohridski Bitola, Macedonia, yDepartment of Veterinary Pathology and zDepartment of Forensic and State Veterinary Medicine, University of Zagreb, Croatia Introduction: Epithelialemesenchymal transition (EMT), as defined by loss of epithelial characteristics and gain of a mesenchymal phenotype, has been reported in human and canine mammary tumours, but similar studies in feline mammary tumours have not been performed. EMT can be induced or regulated by various growth and differentiation factors, among which TGF-b has received much attention. The aims of this study were to evaluate loss of epithelial and gain of mesenchymal markers in neoplastic epithelial cells of feline mammary tumours and to assess possible correlation with expression of TGF-b. Materials and Methods: Twenty-seven hyperplastic and neoplastic feline mammary gland lesions were selected from the archive of the Department of Veterinary Pathology, Zagreb (four benign lesions, three grade I carcinomas, eight grade II and 12 grade III carcinomas) in order to evaluate immunohistochemical expression of cytokeratin AE1/AE3, E-cadherin, vimentin and TGF-b. One-way ANOVA with post-hoc Tukey’s test and Spearman’s rank correlation coefficient were used for statistical analysis. Results: Generally, loss of cytokeratin and E-cadherin and gain of vimentin were more frequently observed in carcinomas of higher malignancy grade compared with benign lesions. However, the correlation between each marker showed only positive correlation between loss of E-cadherin and gain of vimentin (r 5 0.69, P ! 0.05) in grade II carcinomas. The expression of TGF-b was significantly higher in carcinomas of grades II and III compared with grade I (P ! 0.05). Conclusions: These findings indicate the occurrence of characteristic changes suggestive of EMT in feline mammary carcinomas and a possible role for TGF-b in this process.
ESVP, ECVP and NSVP Proceedings 2015
EXPRESSION OF THE PLURIPOTENCY FACTOR OCT4 IN CUTANEOUS MAST CELL TUMOURS T.H.M. Vargas *, L.H. Pulz *, C.N. Barra *, K.G. Cadrobbi *, G.C. Huete *, A.T. Nishiya y, S.R. Kleeb z, J.G. Xavier z and R.F. Strefezzi* *Laboratorio de Oncologia Comparada e Translacional, Universidade de S~ao Paulo, yUniversidade Anhembi-Morumbi and zUniversidade Metodista de S~ao Paulo, Brazil Introduction: Mast cell tumours (MCTs) comprise about 20% of the neoplasms affecting the skin of dogs, and are considered one of the major therapeutic challenges by veterinary oncologists. OCT4 is related to self-renewal and its expression can be detected in normal stem cells as well as in cancer. Cancer stem cells are believed to initiate and maintain the neoplastic cell population. These ‘tumour initiating cells’ are also associated with malignancy and resistance to chemotherapy. The aims of the present work were to investigate the immunoexpression of OCT4 in canine cutaneous MCTs and evaluate associations with histopathological grades, mortality and postsurgical survival. Materials and Methods: Twenty-eight cases of canine cutaneous MCTs were selected. The dogs were treated surgically and did not receive any adjuvant therapy. OCT4 expression was characterized by immunohistochemistry using an anti-OCT4 primary antibody (Santa Cruz Biotechnology, SC-5279). For statistical analysis, only nuclear labelling was considered positive. Results: Thirteen cases showed nuclear and cytoplasmic positivity and eight cases showed cytoplasmic labelling with few scattered positive nuclei. Cytoplasmic labelling was observed in another six MCTs and one case was negative for OCT4. OCT4 expression was not associated with the histopathological grading systems for MCTs, diseaserelated mortality or post-surgical survival. Conclusions: There are different patterns of OCT4 expression in MCTs and nuclear positivity is not an independent marker for this neoplasm. In order to confirm these observations, further studies are needed to evaluate the expression of specific isoforms of the protein.
J. Comp. Path. 2016, Vol. 154, 58e123
AN IMMUNOHISTOCHEMICAL STUDY OF EPITHELIALeMESENCHYMAL TRANSITION IN FELINE MAMMARY TUMOURS N. Karabolovski *, A. Gudan Kurilj y, K. Severin z, y staric-Zuckermann y, L. Medven y, M. Hohsteter , I.-C. So Grabarevicy B. Artukovic y and Z. *Department of Veterinary Pathology, University St. Climent Ohridski Bitola, Macedonia, yDepartment of Veterinary Pathology and zDepartment of Forensic and State Veterinary Medicine, University of Zagreb, Croatia Introduction: Epithelialemesenchymal transition (EMT), as defined by loss of epithelial characteristics and gain of a mesenchymal phenotype, has been reported in human and canine mammary tumours, but similar studies in feline mammary tumours have not been performed. EMT can be induced or regulated by various growth and differentiation factors, among which TGF-b has received much attention. The aims of this study were to evaluate loss of epithelial and gain of mesenchymal markers in neoplastic epithelial cells of feline mammary tumours and to assess possible correlation with expression of TGF-b. Materials and Methods: Twenty-seven hyperplastic and neoplastic feline mammary gland lesions were selected from the archive of the Department of Veterinary Pathology, Zagreb (four benign lesions, three grade I carcinomas, eight grade II and 12 grade III carcinomas) in order to evaluate immunohistochemical expression of cytokeratin AE1/AE3, E-cadherin, vimentin and TGF-b. One-way ANOVA with post-hoc Tukey’s test and Spearman’s rank correlation coefficient were used for statistical analysis. Results: Generally, loss of cytokeratin and E-cadherin and gain of vimentin were more frequently observed in carcinomas of higher malignancy grade compared with benign lesions. However, the correlation between each marker showed only positive correlation between loss of E-cadherin and gain of vimentin (r 5 0.69, P ! 0.05) in grade II carcinomas. The expression of TGF-b was significantly higher in carcinomas of grades II and III compared with grade I (P ! 0.05). Conclusions: These findings indicate the occurrence of characteristic changes suggestive of EMT in feline mammary carcinomas and a possible role for TGF-b in this process.