OJVM  Vol.2 No.4 , December 2012
Spontaneous Mammary Carcinomas in Female Dogs: Association between Immunohistochemical Degrees of Neoplasia Aggressiveness and Residual Pyrethroids
Abstract: Of the tumors diagnosed in the female dogs have the highest mammary neoplasias incidence. These neoplasias can be influenced by environmental contaminants. Despite evidence of pyrethroid toxicity, carcinogenic potential has not yet been sufficiently elucidated, there is a need to investigate their involvement in mammary tumor. In previous studies, pyrethroid residues were detected in female dogs with mammary neoplasia, however was not investigate the influence of this insecticide in the genesis and aggressiveness of mammary cancer. This study aimed to investigate possible relations between pyrethroid residues and aggressiveness of mammary carcinoma in female dogs. Fifty selected female dogs were divided into five groups of 10 animals each: the Control group, female dogs without mammary neoplasia; the groups Luminal A, Luminal B, HER-2 Superexpression and Basal were constituted by female dogs that presented inguinal mammary carcinoma classified immunohistochemically. The aggressiveness of carcinomas was evaluated by immunohistochemistry (HER-2, p63, estrogen receptor). Residual concentrations of the pyrethroids from the mammary gland and fat tissue adjacent to it were determined by HPLC. Data were analyzed by Chi-Square test. Of the all animals, six presented residues of pyrethroids in mammary samples and 10 presented it in fat tissue samples. There was no statistical evidence that pyrethroids are involved in mammary carcinoma aggressiveness in female dogs.
Cite this paper: M. Moleta Colodel, I. Ferreira, V. Maria Villamil Martins, A. Aparecido Almeida, M. Denise Lopes and N. Sousa Rocha, "Spontaneous Mammary Carcinomas in Female Dogs: Association between Immunohistochemical Degrees of Neoplasia Aggressiveness and Residual Pyrethroids," Open Journal of Veterinary Medicine, Vol. 2 No. 4, 2012, pp. 207-215. doi: 10.4236/ojvm.2012.24033.

[1]   H. L. Cameron and W. G. Foster, “Developmental and Lactational Exposure to Dieldrin Alters Mammary Tumorigenesis in Her2/Neu Transgenic Mice,” Phos one, Vol. 4, 2009, pp. 1-8.

[2]   R. Klopfleisch, D. Lenze, M. Hummel, and A. D. Gruber, “Metastatic Canine Mammary Carcinomas Can Be Identified by a Gene Expression Profile That Partly Overlaps with Human Breast Cancer Profiles,” BMC Cancer, Vol. 10, 2010, p. 618. doi:10.1186/1471-2407-10-618

[3]   J. W. Fanton and S. J. Withrow, “Canine Mammary Neoplasia: An Overview,” California Veterinary Medical Association. Vol. 7, 1981, pp. 12-16.

[4]   E. G. Mac Ewen and S. J. Withrow, “Tumors of the Mammary Gland,” In: S. J. Withrow and Mac Ewen, Ed., Small Animal Clinical Oncology, Philadelphia, W. B. Saunders Co, 1996, pp: 356-372.

[5]   Canadian Cancer Society, Statistics Canada, Provincial/Territorial Cancer Registries, Public Health Agency of Canada, “Canadian Cancer Statistics,” 2009. http://www. cancer. ca/canada-wide/about%20cancer/cancer% 20statistics

[6]   Australian Institute of Health and Welfare & Australasian Association of Cancer Registries 2010, “Cancer in Australia 2010: An Overview,” Cancer Series No. 60, Australian Institute of Health and Welfare, Canberra, 2010.

[7]   INCA—Instituto Nacional do Cancer. Brasil. Ministério Da Saúde, “Estimativa 2010: Incidence De Cancer No Brasil,” Independent Networks Cooperative Association, Rio de Janeiro, 2009. http://www. inca. gov. br/estimativa/2010/estimativa2009 1201. pdf

[8]   C. M. Perou, T. Sorlie, M. B. Eisen, M. Van De Rijn, S. S. Jeffrey, C. A. Rees, J. R. Pollack, D. T. Ross, H. Johnsen, L. A. Akslen, E. Flugel, A. Pergamenchikov, C. Williams, S. X. Zhu, P. E. Lùnning, A. Bùrresen-Dale, P. O. Brown and D. Botstein, “Molecular Portraits of Human Breast Tumours,” Nature, Vol. 406, No. 6797, 2000, pp. 747-752. doi:10.1038/35021093

[9]   T. Sorlie, C. M. Perou, R. Tibshirani, T. Aas, S. Geisler, H. Johnsen, T. Hastie, M. B. Eisen, M. Van De Rijn, S. S. Jeffrey, T. Thorsen, H. Quist, J. C. Matese, P. O. Brown, D. Botstein, P. Eystein Lonning and A. L. Borresen-Dale, “Gene Expression Patterns of Breast Carcinomas Distinguish Tumor Subclasses with Clinical Implications,” Proceedings of the National Academy of Sciences, Vol. 98, No. 19, 2001, pp. 10859-10874. doi:10.1073/pnas.191367098

[10]   T. Sorlie, “Molecular Portraits of Breast Cancer: Tumour Subtypes as Distinct Disease Entities,” European Journal of Cancer & Clinical Oncology, Vol. 40, No. 18, 2004, pp. 2667-2675.

[11]   T. Sorlie, Y. Wang, C. Xiao, H. Johnsen, B. Naume, R. R. Samaha, and A. Borresen-Dale, “Distinct Molecular Mechanisms Underlying Clinically Relevant Subtypes of Breast Cancer: Gene Expression Analyses Cross Three Different Platforms,” BMC Genomics, Vol. 7, 2006, pp. 127. doi:10.1186/1471-2164-7-127

[12]   A. Gama, A. Alves, and F. Schmitt, “Identification of Molecular Phenotypes in Canine Mammary Carcinomas with Clinical Implications: Application of the Human Classification,” Virchows Archiv, Vol. 453, No. 2, 2008, pp. 123-132. doi:10.1007/s00428-008-0644-3

[13]   F. Sassi, C. Benazzi, G. Castellani and G. Sarli, “Molecular-Based Tumour Subtypes of Canine Mammary Carcinomas Assessed by Immunohistochemistry,” BMC Veterinary Research, Vol. 6, 2010, p. 5. doi:10.1186/1746-6148-6-5

[14]   M. L. Z. Dagli, “The Search for Suitable Prognostic Markers for Canine Mammary Tumors: A Promising Outlook,” Veterinary Journal, Vol. 177, No. 1, 2008, pp. 3-5. doi:10.1016/j.tvjl.2007.10.015

[15]   S. M. Barlow, F. M. Sullivan and J. Lines, “Risk Assessment of the Use of Deltamethrin on Bednets for the Prevention of Malaria,” Food and Chemical Toxicology, Vol. 39, No. 5, 2001, pp. 407-422. doi:10.1016/S0278-6915(00)00152-6

[16]   A. Anadón, M. R. Martínez-Larranaga and M. A. Martínez, “Use and Abuse of Pyrethrins and Synthetic Pyrethroids in Veterinary Medicine,” Veterinary Journal, Vol. 182, No. 1, 2009, pp. 7-20. doi:10.1016/j.tvjl.2008.04.008

[17]   D. M. Soderlund, J. M. Clark, L. P. Sheets, L. S. Mullin, V. J. Piccirillo, D. Sargent, J. T. Stevensand, M. L. Weiner, “Mechanisms of Pyrethroid Neurotoxicity: Implications for Cumulative Risk Assessment,” Toxicology, Vol. 171, No. 1, 2002, pp. 3-59. doi:10.1016/S0300-483X(01)00569-8

[18]   M. J. Crawford, A. Croucher and D. H. Hutson, “Metabolism of Cis- and Trans-Cypermethrin in Rats. Balance and Tissue Retention Study,” Journal of Agricultural and Food Chemistry. Vol. 29, No. 1, 1981, pp. 130-135. doi:10.1021/jf00103a033

[19]   K. E. Appel, and S. Gericke, “Zur Neurotoxizit?t und Toxikokinetik von Pyrethroiden,” Bundesgesundheitsblatt, Vol. 36, No. 6, 1993, pp. 219-228.

[20]   M. C. R. Alavanja, M. Dosemeci, C. Samanic, J. Lubin, C. F. Lynch, C. Knott, C. Knott, J. Barker, J. á. Hoppin, D. P. Sandler, J. Coble, K. Thomas, and A. Blair, “Pesticides and Lung Cancer Risk in the Agricultural Health Study Cohort,” American Journal of Epidemiology, Vol. 160, No. 9, 2004, pp. 876-885. doi:10.1093/aje/kwh290

[21]   W. J. Lee, D. P. Sandle, A. Blair, C. Samanic, A. J. Cross, and M. C. R. Alavanja, “Pesticide Use And Colorectal Cancer Risk in the Agricultural Health Study,” International Journal of Cancer, Vol. 121, No. 2, 2007, pp. 339-346. doi:10.1002/ijc.22635

[22]   G. Andreotti, L. E. Freeman, L. Hou, J. Coble, J. Rusiecki, J. á. Hoppin, D. T. Silverman, and M. C. Alavanja, “Agricultural Pesticide Use and Pancreatic Cancer Risk in the Agricultural Health Study Cohort,” International Journal of Cancer, Vol. 124, No. 10, 2009, pp. 2495-2500. doi:10.1002/ijc.24185

[23]   L. K. Dennis, C. F. Lynch, D. P. Sandler and M. C. R. Alavanja, “Pesticide Use And Cutaneous Melanoma in Pesticide Applicators ?In the Agricultural Heath Study,” Environmental Health Perspectives, Vol. 118, No. 6, 2010, pp. 812-817. doi:10.1289/ehp.0901518

[24]   L. M. Brown, A. Blair, R. Gibson, G. D. Everett, D. P. Cantor, L. M. Schuman, L. F. Burmeister, S. F. Van Lier, and F. Dick, “Pesticide Exposures and Other Agricultural Risk Factors for Leukemia Among Men in Iowa and Minnesota,” Cancer Research, Vol. 50, No. 20, 1990, pp. 6585-6591.

[25]   M. C. R. Alavanja, C. Samanic, M. Dosemeci, J. Lubin, R. Tarone, C. F. Lynch, C. Knott, K. Thomas, J. á. Hoppins, J. Barker, J. Coble, D. P. Sandler and A. Blair, “Use of Agricultural Pesticides and Prostate Cancer Risk in the Agricultural Health Study cohort,” American Journal of Epidemiology, Vol. 157, No. 9, 2003, pp. 800-814. doi:10.1093/aje/kwg040

[26]   J. á Rusiecki, R. Patel, S. Koutros, L. Beane-Freeman, O. Landgren, M. R. Bonner, J. Coble, J. Lubin, A. Blair, J. á. Hoppin and M. C. Alavanja, “Cancer incidence Among Pesticide Applicators Exposed to Permethrin in the Agricultural Health Study,” Environmental Health Perspectives, Vol. 117, No. 4, 2009, pp. 581-586.

[27]   C. M. Parker, D. R. Patterson, G. A. Van Gelder, E. B. Gordon, M. G. Valerio and W. C. Hall, “Chronic Toxicity and Carcinogenicity Evaluation of Fenvalerate in Rats,” Journal of Toxicology and Environmental Health, Vol. 13, No. 1, 1984, pp. 83-97. doi:10.1080/15287398409530483

[28]   L. S. Engel, D. A. Hill, J. á. Hoppin, J. H. Lubin, C. F. Lynch, J. Pierce, C. Samanic, D. P. Sandler, A. Blair and M. C. R. Alavanja, “Pesticide Use and Breast Cancer Risk among Farmers’ Wives in the Agricultural Health Study,” American Journal of Epidemiology, 161, No. 2, 2005, 121-135. doi:10.1093/aje/kwi022

[29]   F. H. E. Andrade, F. C. Figueiroa, P. R. O. Bersano, D. Z. Bissacot and N. S. Rocha, “Malignant Mammary Tumor in Female Dogs: Environmental Contaminants,” Diagnostic Pathology, Vol. 5, 2010, p. 45. doi:10.1186/1746-1596-5-45

[30]   M. H. Bariani and N. S. Rocha, “Residues of Pyrethroids in the Adipose Tissue Adjacent to Spontaneous Mammary Carcinoma in Female Dogs,” Revista Científica Eletr?nica de Medicina Veterinária, Vol. 8, No. 15, 2010.

[31]   S. W. Allen, K. W. Prasse, and E. A. Mahaffey, “Cytologic Differentiation of Benign from Malignant Canine Mammary Tumors,” Veterinary Pathology, Vol. 23, No. 6, 1986, pp. 649-655.

[32]   W. Misdorp, R. W. Else, E. Hellman and T. P. Lipscomb, “Histological Classification of Mammary Tumors of the Dog and the Cat,” Vol. 7, Armed Forces Institute of Pathology, Washington DC, 1999, p. 58.

[33]   F. C. Schmitt, M. J. Bento, and I. Amendoeira, “Estimation of Estrogen Receptor Content in Fine-Needle Aspirates from Breast Cancer Using the Monoclonal Antibody 1D5 and Microwave Oven Processing: Correlation with Paraffin Embedded and Frozen Sections Determinations,” Diagnostic Cytopathology, Vol. 13, No. 4, 1995, pp. 347-351. doi:10.1002/dc.2840130417

[34]   R. Bhargava, N. N. Esposito, and D. J. Dabbs, “Immunohistology of the Breast,” In: D. J. Dabbs, Eds., Diagnostic Immunohistochemistry Theranostic and Genomic Applications, WB Saunders Co., Philadelphia, pp. 763-819, 2010.

[35]   D. Z. Bissacot, and I. Vassilieff, “HPLC Determination of Flumethrin, Deltamethrin, Cypermethrin and Cyhalothrin Residues in Milk and Blood of Lactating Dairy Cows,” Journal of Analytical Toxicology, Vol. 21, No. 5, 1997, pp. 397-402.

[36]   G. W. Snedecor and W. G. Cochran, “Statistical Methods,” Iowa State University Press, Ames, 1994.

[37]   International Agency for Research Cancer—IARC, “Overall Evaluations of Carcinogenicity to Humans”. http://monographs. iarc. fr/ENG/Monographs/vol53/mono 53-10. pdf

[38]   United States Environmental Protection Agêncy—US EPA, “Permethrin & Resmethrin (Pyrethroids). TEACH Chemical Summary. Toxicity and Exposure Assessment for Children’s Health”. http://www. epa. gov/teach/chem_summ/pyrethroid_summary. pdf

[39]   J. R. P. Cabral, D. Galendo, M. Laval and N. Lyandrat, “Carcinogenicity Studies with Deltamethrin in Mice and Rats,” Cancer Letter, Vol. 49, No. 2, 1990, pp. 147-152. doi:10.1016/0304-3835(90)90151-M

[40]   Y. Deguchi, T. Yamada, Y. Hirose, H. Nagahori, M. Kushidaj, K. Sumida, T. Sukata, Y. Tomigahara, K. Nishioka, S. Uwagawa, S. Kawamura and Y. Okuno, “Mode of Action Analysis for the Synthetic Pyrethroid Metofluthrin-Induced Rat Liver Tumors: Evidence for Hepatic CYP2B Induction and Hepatocyte Proliferation,” Toxicological Sciences, Vol. 108, No. 1, 2009, pp. 69-80. doi:10.1093/toxsci/kfp006