Microvessel density assessment in canine mammary carcinomas as a predictive factor for metronomic chemotherapy
DOI:
https://doi.org/10.5433/1679-0359.2019v40n5p1849Keywords:
Angiogenesis, Antiangiogenic chemotherapy, Female dog, Mammary tumor.Abstract
The canine mammary tumor is the neoplasia that most commonly affects intact female dogs (not spayed) in routine veterinary practice. Canine mammary tumor therapy is a challenge because only few effective treatments have been described for high-grade tumors in veterinary medicine. One such therapeutic option that slows down tumor growth is metronomic chemotherapy (MC), a therapeutic modality that acts by decreasing tumor angiogenesis. Quantification of intratumoral microvessel density (MVD) has been proposed as a means to evaluate the effectiveness of MC in human and canine tumors. In this study, MVD is proposed as a predictive factor for the effectiveness of MC in canine mammary tumors. Twenty female dogs with mammary carcinoma were equally distributed into a mastectomy group treated only with mastectomy, and a MC group treated with MC (cyclophosphamide and piroxicam) orally and daily for 28 days followed by mastectomy. Mammary tumors were classified and graded histologically. MVD was ascertained by CD31 immunostaining. The analysis showed statistically significant difference in MVD scores between groups, corroborating a quantitative reduction in tumor microvasculature in the group treated with MC. Our findings suggest that MVD may be an important predictive factor for the selection of female dogs with malignant mammary tumors that may benefit from MC.Downloads
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References
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BIESAGA, B.; NIEMIEC, J.; ZIOBRO, M. Microvessel density and status of p53 protein as potential prognostic factors for adjuvant anthracycline chemotherapy in retrospective analysis of early breast cancer patients group. Pathology and Oncology Research, Dordrecht, v. 18, n. 4, p. 949-960, 2012. DOI: 10.1007/s12253-012-9525-9
BILLER, B. Metronomic chemotherapy in veterinary patients with cancer: rethinking the targets and strategies of chemotherapy. Veterinary Clinics of North America: Small Animal Practice, Amsterdam, v. 44, n. 5, p. 817-29, 2014. DOI: 10.1016/j.cvsm.2014.05.003
BROWDER, T.; BUTTERFIELD, C. E.; KRALING, B.M.; SHI, B.; MARSHALL, B.; O’REILLY, M. S.; FOLKMAN, J. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Research, Philadelphia, v. 60, n. 7, p. 1878-1886, 2000.
CASSALI, G. D.; LAVALLE, G. E.; FERREIRA, E.; ESTRELA-LIMA, A.; NARDI, A. B. de; GHEVER, C.; SOBRAL, R. A.; AMORIM, R. L.; OLIVEIRA, L. O.; SUEIRO, F. A. R.; BESERRA, H. E. O.; BERTAGNOLLI, A. C.; GAMBA, C. O.; DAMASCENO, K. A.; CAMPOS, C. B.; ARAUJO, M. R.; CAMPOS, L. C.; MONTEIRO, L. N.; NUNES, F. C.; HORTA, R. S.; REIS, D. C.; LUVIZOTTO, M. C. R.; MAGALHÃES, G. M.; RAPOSO, J. B.; FERREIRA, A. M. R.; TANAKA, N. M.; GRANDI, F.; UBUKATA, R.; BATSCHINSKI, K.; TERRA, E. M.; SALVADOR, R. C. L.; JARK, P. C.; DELECRODI, J. E. R.; NASCIMENTO, N. A.; SILVA, D. N.; SILVA, L. P.; FERREIRA, K. C. R. S.; FREHSE, M. S.; DI SANTIS, G. W.; SILVA, E. O.; GUIM, T. N.; KERR, B.; CINTRA, P. P.; SILVA, F. B. F.; LEITE, J. S.; MELLO, M. F. V.; FERREIRA, M. L. G.; FUKUMASU, H.; SALGADO, B. S.; TORRES, R. Consensus for the diagnosis, prognosis and treatment of canine mammary tumors - 2013. Brazilian Journal of Veterinary Pathology, Belo Horizonte, v. 7, n. 2, p. 38-69, 2014.
CHAN, C. M.; FRIMBERGER, A. E.; MOORE, A. S. Incidence of sterile hemorrhagic cystitis in tumor-bearing dogs concurrently treated with oral metronomic cyclophosphamide chemotherapy and furosemide: 55 cases (2009-2015). Journal of the American Veterinary Medical Association, New York, v. 249, n. 12, p. 1408-1414, 2016. DOI: 10.2460/javma.249.12.1408
EGENVALL, A.; BONNETT, B. N.; OHAGEN, P.; OLSON, P.; HEDHAMMAR, A.; VON EULER, H. Incidence of and survival after mammary tumors in a population of over 80,000 insured female dogs in Sweden from 1995 to 2002. Preventive Veterinary Medicine, Amsterdam, v. 69, n. 1-2, p. 109-127, 2005. DOI: 10.1016/j.prevetmed.2005.01.014
ELMSLIE, R. E.; GLAWE, P.; DOW, S. W. Metronomic therapy with cyclophosphamide and piroxicam effectively delays tumor recurrence in dogs with incompletely resected soft tissue sarcomas. Journal of Veterinary Internal Medicine, Greenwood Village, v. 22, n. 6, p. 1373-1379, 2008. DOI: 10.1111/j.1939-1676.2008.0179.x
GASPARINI, G.; BIGANZOLI, E.; BONOLDI, E.; MORABITO, A.; FANELLI, M.; BORACCHI, P. Angiogenesis sustains tumor dormancy in patients with breast cancer treated with adjuvant chemotherapy. Breast Cancer Research and Treatment, New York, v. 65, n. 1, p. 71-75, 2001. DOI: 10.1023/A:1006476401801
GOBELLO, C.; DE LA SOTA, R. L.; GOYA, R. G. A review of canine pseudocyesis. Reproduction in Domestic Animals, Oxford, v. 36, n. 6, p. 283-288, 2001. DOI: 10.1046/j.1439-0531.2001.00322.x
HLATKY, L.; HAHNFELDT, P.; FOLKMAN, J. Clincal application of antiangiogenic therapy: microvessel density, what it does and doesn´t tell us. Journal of the National Cancer Institute, Oxford, v. 94, n. 12, p. 883-893, 2002. DOI: 10.1093/jnci/94.12.883
JAKAB, C.; HALÁSZ, J.; KISS, A.; SCHAFF, Z.; SZÁSZ, A. M.; RUSVAI, M.; TÓTH, Z. A.; KULKA, J. Evaluation of microvessel density (MVD) in canine mammary tumours by quantitative immunohistochemistry of the claudin-5 molecule. Acta Veterinaria Hungarica, Budapest, v. 56, n. 4, p. 495-510, 2008. DOI: 10.1556/AVet.56.2008.4.7
LUNA, L. G. Rotine staining procedures. In: LUNA, L. G. (Ed.). Manual of histologic staining methods of the armed forces institute of pathology. New York: McGrae-Hill Book, 1968. cap. 4, p. 32-46.
MARCHETTI, V.; GIORGI, M.; FIORAVANTI, A.; FINOTELLO, R.; CITI, S.; CANU, B.; ORLANDI, P.; DI DESIDERO, T.; DANESI, R.; BOCCI, G. First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study. Investigational New Drugs, New York, v. 30, n. 4, p. 1725-1730, 2012. DOI: 10.1007/s10637-011-9672-y
MARTIN, L.; GREEN, B.; RENSHAW, C.; LOWE, D.; RUDLAND, P.; LEINSTER, S. J.; WINSTANLEY, J. Examining the technique of angiogenesis assessment in invasive breast cancer. British Journal of Cancer, London, v. 76, n. 8, p. 1046-1054, 1997. DOI: 10.1038/bjc.1997.506
MISDORP, W.; ELSE, R. W.; HELLMÉN, E.; LIPSCOMB, E. Who histological classification of mammary tumors of the dog and cat. Washington: Armed Forces Institute of Pathology, 1999. 58 p.
MUTSAERS, A. J. Metronomic chemotherapy. Topics in Companion Animal Medicine, Amsterdam, v. 24, n. 3, p. 137-143, 2009. DOI: 10.1053/j.tcam.2009.03.004
OWEN, L. N. The TNM classification of tumors in domestic animals. Geneva: World Health Organization, 1980. 53 p.
SCHMITT, F. C.; SOARES, R.; CIRNES, L.; SERUCA, R. P53 in breast carcinomas: association between presence of mutation n and immunohistochemical expression using a semiquantitative approach. Pathology - Research and Practice, Amsterdam, v. 194, n. 12, p. 815-819, 1998. DOI: 10.1016/S0344-0338(98)80083-6
STRAW, R. C. Treatment of mammary gland tumors and perianal neoplasia. In: THE NORTH AMERICAN VETERINARY CONFERENCE, 2005, Orlando. Proceedings… Orlando: NAVC, 2005. p. 672-675.
WEAVER, D. L. Pathology evaluation of sentinel lymph nodes in breast cancer: protocol recommendations and rationale. Modern Pathology, London, v. 23, n. 2, p. 26-32, 2010. DOI: 10.1038/modpathol.2010.36
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2019-07-04
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Ferrari, A. R. M., Ferrari, H. F., Carreira, V. S., Frigério, E. D., Luvizotto, M. C. R., & Andrade, A. L. de. (2019). Microvessel density assessment in canine mammary carcinomas as a predictive factor for metronomic chemotherapy. Semina: Ciências Agrárias, 40(5), 1849–1856. https://doi.org/10.5433/1679-0359.2019v40n5p1849
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