View More View Less
  • 1 Gazi University Laboratory, Animal Breeding and Experimental Research Centre, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey
  • 2 Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey
  • 3 Faculty of Veterinary Medicine, Ondokuz Mayis University, Kurupelit, Samsun, Turkey
  • 4 Faculty of Veterinary Medicine, Ankara University, Diskapi, Ankara, Turkey
  • 5 Faculty of Veterinary Medicine, Ankara University, Diskapi, Ankara, Turkey
  • 6 Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $836.00

The aim of the present study was to investigate the relationship between the expression of iNOS, COX-2 and VEGF mRNA levels and malignancy degree in canine malignant mammary tumours. Thirty-five bitches presented with the complaint of mammary masses, aged 6–10 years and representing different breeds, were used. The expressions of iNOS, COX-2 and VEGF mRNA levels were significantly higher in both benign and malignant tumours than in the adjacent nonneoplastic mammary glands (P < 0.05). The iNOS, COX-2 and VEGF mRNA expression levels of grade 2 tumours were higher than those of grade 1 tumours; however, the highest expression levels were detected in grade 3 tumours. Thus, increased iNOS, COX-2 and VEGF gene mRNA levels were found to be related with the histological grade of malignancy in dogs with mammary tumours.

  • Bing, R. J., Miyataka, M., Rich, K. A., Hanson, N., Wang, X., Slosser, H. D. and Shi, S. R. (2001): Nitric oxide, prostanoids, cyclooxygenase, and angiogenesis in colon and breast cancer. Clin. Canc. Res. 7, 33853392.

    • Search Google Scholar
    • Export Citation
  • Cianfrocca, M. and Goldstein, L. J. (2004): Prognostic and predictive factors in early-stage breast cancer. Oncologist 9, 606616.

  • Costa, C., Soares, R., Reis-Filho, J. S., Leitaõ, D., Amendoeira, I. and Schmitt, F. C. (2002): Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer. J. Clin. Pathol. 55, 429434.

    • Search Google Scholar
    • Export Citation
  • Denkert, C., Winzer, K. J., Müller, B. M., Weichert, W., Pest, S., Kobel, M., Kristiansen, G., Reles, A., Siegert, A., Guski, H. and Hauptmann, S. (2003): Elevated expression of cyclooxygenase- 2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma. Cancer 97, 29782987.

    • Search Google Scholar
    • Export Citation
  • Dore, M., Lanthier, I. and Sirois, J. (2003): Cyclooxygenase-2 expression in canine mammary tumours. Vet. Pathol. 40, 207212.

  • Elston, C. W. and Ellis, I. O. (1998): Assessment of histological grade. In: Elston, C. W. and Ellis, I. O. (eds) The Breast. Vol. 13. Churchill Livingstone, Edinburgh. pp. 356384.

    • Search Google Scholar
    • Export Citation
  • Ferreira, E., Bertagnolli, A. C., Cavalcanti, M. F., Schmitt, F. C. and Cassali, G. D. (2009): The relationship between tumour size and expression of prognostic markers in benign and malignant canine mammary tumours. Vet. Comp. Oncol. 7, 230235.

    • Search Google Scholar
    • Export Citation
  • Förstermann, U., Closs, E. I., Pollock, J. S., Nakane, M., Schwarz, P., Gath, I. and Kleinert, H. (1994): Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension 23, 11211131.

    • Search Google Scholar
    • Export Citation
  • Goldschmidt, M., Peña, L., Rasotto, R. and Zappulli, V. (2011): Classification and grading of canine mammary tumors. Vet. Pathol. 48, 117131.

    • Search Google Scholar
    • Export Citation
  • Guimaraes, M. J., Carvalho, M. I., Pires, I., Prada, J., Gonzalez, Gil A., L opes, C. and Queiroga, F. L. (2014): Concurrent expression of cyclo-oxygenase-2 and epidermal growth factor receptor in canine malignant mammary tumours. J. Comp. Path. 150, 2734.

    • Search Google Scholar
    • Export Citation
  • Heller, D. A., Clifford, C. A., Goldschmidt, M. H., Holt, D. E., Shofer, F.S., Smith, A. and Sorenmo, K. U. (2005): Cyclooxygenase-2 expression is associated with histologic tumour type in canine mammary carcinoma. Vet. Pathol. 42, 776780.

    • Search Google Scholar
    • Export Citation
  • Howe, L. R. (2007): Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Res. 9, 210.

  • Islam, M. S., Matsumoto, M., Hidaka, R., Miyoshi, N. and Yasuda, N. (2012): Expression of NOS and VEGF in feline mammary tumours and their correlation with angiogenesis. Vet. J. 192, 338344.

    • Search Google Scholar
    • Export Citation
  • Johnston, S. D., Kustritz, M. V. R. and Olson, P. N. S. (2001): Canine and Feline Theriogenology. W. B. Saunders, Philadelphia.

  • Karayannopoulou, M., Kaldrymidou, E., Constantinidis, T. C. and Dessiris, A. (2005): Histological grading and prognosis in dogs with mammary carcinomas: Application of a human grading method. J. Comp. Path. 133, 246252.

    • Search Google Scholar
    • Export Citation
  • Knowles, R. G. and Moncada, S. (1994): Nitric oxide synthases in mammals. Biochem. J. 298, 249258.

  • Lala, P. K. and Chakraborty, C. (2001): Role of nitric oxide in carcinogenesis and tumour progression. Lancet. Oncol. 3, 149156.

  • Lechner, M., Lirk, P. and Rieder, J. (2005): Inducible nitric oxide synthase (iNOS) in tumor biology: The two sides of the same coin. Semin. Cancer Biol. 15, 277289.

    • Search Google Scholar
    • Export Citation
  • Millanta, F., Citi, S., Della Santa, D., Porciani, M. and Poli, A. (2006): COX-2 expression in canine and feline invasive mammary carcinomas: correlation with clinicopathological features and prognostic molecular markers. Breast Canc. Res. Treat. 98, 115120.

    • Search Google Scholar
    • Export Citation
  • Moulton, J. E. (1990): Tumors of the skin and soft tissues. In: Moulton, J. E. (ed.) Tumors in Domestic Animals. Third edition. University of California Press, Los Angeles, CA. p. 23.

    • Search Google Scholar
    • Export Citation
  • Niu, X. J., Wang, Z. R., Wu, S. L., Geng, Z.M., Zhang, Y. F. and Qing, X. L. (2004): Relationship between inducible nitric oxide synthase expression and angiogenesis in primary gallbladder carcinoma tissue. World J. Gastroenterol. 10, 725728.

    • Search Google Scholar
    • Export Citation
  • Owen, L. N. (1980): TNM Classification of Tumours in Domestic Animals. First edition. World Health Organization, Geneva. pp. 253.

  • Perez Alenza, M. D., Pena, L., Nieto, A. I. and Castano, M. (1997): Clinical and pathological prognostic factors in canine mammary tumors. Ann. Ist. Super Sanita. 33, 581585.

    • Search Google Scholar
    • Export Citation
  • Pfaffl, M. W., Horgan, G. W. and Dempfle, L. (2002): Relative expression software tool (REST) for groupwise comparison and statistical analysis of relative expression results in real-time PCR. Nucl. Acids Res. 30, e36.

    • Search Google Scholar
    • Export Citation
  • Philibert, J. C., Snyder, P. W., Glickman, N., Glickman, L.T., Knapp, D. W. and Waters, D. J. (2003): Influence of host factors on survival in dogs with malignant mammary gland tumors. J. Vet. Int. Med. 17, 102106.

    • Search Google Scholar
    • Export Citation
  • Queiroga, F. L., Alves, A., Pires, I. and Lopes, C. (2007): Expression of COX-1 and COX-2 in canine mammary tumours. J. Comp. Path. 136, 177185.

    • Search Google Scholar
    • Export Citation
  • Queiroga, F. L., Perez-Alenza, M. D., Silvan, G., Peña, L., Lopes, C. and Illera, J. C. (2005): COX- 2 levels in canine mammary tumors, including inflammatory mammary carcinoma: clinicopathological features and prognostic significance. Anticanc. Res. 25, 42694276.

    • Search Google Scholar
    • Export Citation
  • Queiroga, F. L., Pires, I., Lobo, L. and Lopes, C. S. (2010): The role of COX-2 expression in the prognosis of dogs with malignant mammary tumours. Res. Vet. Sci. 88, 441445.

    • Search Google Scholar
    • Export Citation
  • Queiroga, F. L., Pires, I., Parente, M., Gregório, H. and Lopes, C. S. (2011): COX-2 overexpression correlates with VEGF and tumour angiogenesis in canine mammary cancer. Vet. J. 189, 7782.

    • Search Google Scholar
    • Export Citation
  • Ranganathan, S., Krishnan, A. and Sivasithambaram, N. D. (2016): Significance of twist and iNOS expression in human breast carcinoma. Mol. Cell. Biochem. 412, 4147.

    • Search Google Scholar
    • Export Citation
  • Restucci, B., Papparella, S., Maiolino, P. and De Vico, G. (2002): Expression of vascular endothelial growth factor in canine mammary tumors. Vet. Pathol. 39, 488493.

    • Search Google Scholar
    • Export Citation
  • Simpson, J. F., Gray, R., Dressler, L. G., Cobau, C. D., Falkson, C. I., Gilchrist, K.W., Pandya, K.J., Page, D. L. and Robert, N. J. (2000): Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189. J. Clin. Oncol. 18, 20592069.

    • Search Google Scholar
    • Export Citation
  • Sorenmo, K. J., Shofer, F. S. and Goldschmidt, M. H. (2000): Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma. J. Vet. Intern. Med. 14, 266270.

    • Search Google Scholar
    • Export Citation
  • Tascene, N., Kismali, G., Vural, S., Karagul, H. and Sel, T. (2012): Serum neopterin, sialic acid and nitric oxide levels in dogs with malignant mammary tumours. Vet. Comp. Oncol. 10, 155159.

    • Search Google Scholar
    • Export Citation
  • Thomsen, L. L., Miles, D. W., Happerfield, L., Bobrow, L.G., Knowles, R. G. and Moncada, S. (1995): Nitric oxide synthase activity in human breast cancer. Br. J. Cancer 72, 4144.

    • Search Google Scholar
    • Export Citation
  • Vakkala, M., Kahlos, K., Lakari, E., Paakko, P., Kinnula, V. and Soini, Y. (2000): Inducible nitric oxide synthase expression, apoptosis, and angiogenesis in in situ and invasive breast carcinomas. Clin. Cancer Res. 6, 24082416.

    • Search Google Scholar
    • Export Citation
  • Villalobos, A. and Kaplan, L. (2007): Canine and Feline Geriatric Oncology: Honoring the Human–Animal Bond. First edition. Wiley-Blackwell, Iowa. pp. 323.

    • Search Google Scholar
    • Export Citation
  • Williams, C. S., Mann, M. and DuBois, R. N. (1999): The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18, 79087916.

    • Search Google Scholar
    • Export Citation
  • Zafirellis, K., Zachaki, A., Agrogiannis, G. and Gravani, K. (2010): Inducible nitric oxide synthase expression and its prognostic significance in colorectal cancer. APMIS 118, 115124.

    • Search Google Scholar
    • Export Citation