Diagnosis, classification and grading of canine mammary tumours as a model to study human breast cancer: an Clinico-Cytohistopathological study with environmental factors influencing public health and medicine

Cancer Cell International

Farshid Khadivar⁴  Hasti Daraei¹  Alimohammad Bahrami⁶  Danial Kheradmand²  Pegah Kheradmand⁵  Nahid Atyabi³  Javad Javanbakht³  Radmehr Shafiee⁴ 

[1]Department of Environmental Health Engineering, Alborz University of Medical Sciences, Karaj, Iran

[2]MD, Graduate Islamic Azad University of Mashhad, Faculty of Medicine, Mashhad, Iran

[3]Department of Pathology, Faculty of Veterinary Medicine, Tehran University, Tehran, Iran

[4]Faculty of Veterinary Medicine, Tehran University, Tehran, Iran

[5]Semnan University of Medical Science, Faculty of Medicine, Semnan, Iran

[6]MD, Graduate Paraveterinary Faculty of Ilam, University of Ilam, Ilam, Iran

关键词: Tumour;    Mammary glands;    Dog;    Cytohistopathology;    Grading of tumours;   

Others  :  793168
DOI  :  10.1186/1475-2867-13-79

 received in 2013-07-15, accepted in 2013-08-05,  发布年份 2013

【 摘 要 】

Background

The human “Elston and Ellis grading method” was utilized in dogs with mammary tumor to examine its relation to prognosis in this species, based on a 2-year follow-up period. Although cytopathology is widely used for early diagnosis of human neoplasms, it is not commonly performed in veterinary medicine. Our objectives in this study were to identify cytopathology criteria of malignancy for canine mammary tumors and the frequency of different types of mammary lesions and their relationship with histologic grade was investigated. Another aim of this study was to differentiate the simple and adenocarcinoma tumors from the complex or mixed tumor described by Elston and Ellis grading method.

Methods

The study was performed in 15 pure or mixed-breed female dogs submitted to surgical resections of mammary tumours. The mammary tumours were excised by simple mastectomy or regional mastectomy, with or without the superficial inguinal lymph nodes. Female dogs were mainly terriers (9 dogs) or mixed (3 dogs), the 3 other animals were a German shepherd, Dachshund and Pekingese. Before surgical excision of the tumour, FNAC was performed using a 0.6 mm diameter needle attached to a 10 ml syringe held in a standard metal syringe holder. The cytological sample was smeared onto a glass slide and either air-dried for May-Grünwald-stain, or ethanol-fixed for Papanicolaou stain and masses were surgically removed, the tumours were grossly examined and tissue samples were fixed in 10%-buffered-formalin and embedded in paraffin. Sections 4 μm thick were obtained from each sample and H&E stained.

Results

We obtained a correct cytohistological correlation in 14/15 cases (93.3%) when all cytopathological examinations were considered. Of the 15 cases examined, 2(13.3%) had well-differentiated (grade I), 6(40%) had moderately differentiated (grade II) and 7(46.7%) had poorly differentiated (grade III) tumours. Classification of all canine mammary gland lesions revealed 13(86.7%) malignant and 2(13.3%) benign tumors. The histological examination showed that the most common tumor types of mammary glands in bitches were: complex carcinoma, adenocarcinoma, malignant mixed tumour, benign mixed tumour, simple carcinoma– (5/15; 33.3%), (3/15; 20%), (3/15; 20%) and (2/15;13.3%), respectively. Simple carcinoma and cystic hyperplasia were less common - (1/15; 6.7%), and (1/15; 6.7%), respectively. Moreover, the most often tumors occur in inguinal mammary (60%) and abdominal (27%) glands.

Conclusions

Our results demonstrate that, because of the similarity of the cytohistopathological findings in the human and canine mammary gland tumours, it is possible to use the same cytopathological criteria applied in human pathology for the diagnosis of canine mammary gland tumours. Furthemoer, routine use of this human grading method would help the clinician to make a more accurate prognosis in the interests of post-surgical management in dogs with mammary carcinomas. Furthermore, this research will allow a more discriminating classification of mammary tumors and probably has a bearing on cytohistopathology, epidemiology, pathogenesis and prognosis. The most often tumors occur in inguinal mammary (60%) and abdominal (27%) glands. This interesting regional difference may be due to a) the duration of the growth before the diagnosis; b) the age of the dogs; and c) high prevelance of unspayed animals. Moreover, the most common type of tumor was complex carcinoma – 33.3% (5 cases).

【 授权许可】

   
2013 shafiee et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Moe L: Population-based incidence of mammary tumours in some dog breeds. J Reprod Fertil Suppl 2001, 57:439-443.
• [2]Egenvall A, Bonnett BN, 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. Prev Vet Med 2005, 69:109-127.
• [3]Rivera P: Biochemical Markers and Genetic Risk Factors in Canine Tumors. Uppsala: Doctoral Thesis Swedish University of Agricultural Sciences; 2010. http://www.diss-epsilon.slu.se:8080/archive/00002280/01/rivera_p_100503.pdf webcite. Accessed 2010;29.8.11
• [4]Desantis C, Siegel R, Bandi P, Jemal A: Breast cancer statistics. CA Cancer J Clin 2011, 61:409-418.
• [5]Brody RS, Goldschmidt NH, Roszel JR: Canine mammary gland neoplasms. J Am Anim Hosp Assoc 1983, 35(5):1961-1990.
• [6]Brunelle M: Cyclooxygenase-2 expression in normal and neoplastic canine mammary cell lines. Vet Pathol 2006, 43(5):656-666.
• [7]Sorenmo K: Canine mammary gland tumors. Vet Clin Small Anim 2003, 33:573-596.
• [8]Cyrta J, Andreiuolo F, Azoulay S, Balleyguier C, Bourgier C, Mazouni C, Mathieu MC, Delaloge S, Vielh P: Pure and mixed mucinous carcinoma of the breast: fine needle aspiration cytology findings and review of the literature. Cytopathology 2012, 32(6):e64-8.
• [9]de Graaf H, Willemse P, Laddé BE, Van den Bergen HA, Krebber M, Tjabbes T, Sluiter WJ: Evaluation of a cytological scoring system for predicting histological grade and disease-free survival in primary breast cancer. Cytopathology 1994, 5(5):294-300.
• [10]Bofin AM, Lydersen S, Isaksen C, Hagmar BM: Interpretation of fine needle aspiration cytology of the breast: a comparison of cytological, frozen section, and final histological diagnoses. Cytopathology 2004, 15(6):297-304.
• [11]Gupta K, Sood NK, Uppal SK, Mohindroo J, Mahajan S, Raghunath M, Singh K: Epidemiological Studies on Canine Mammary Tumour and its Relevance for Breast Cancer Studies. IOSR Journal of Pharmacy 2012, 2(2):322-333.
• [12]Baker R, Lumsden JH: The mammary gland. In Color Atlas of Cytology of the Dog and Cat. Edited by Baker R, Lumsden JH. St Louis: Mosby; 2000:253-262.
• [13]Paget J: Apud McCARTHY E: Giant-cell tumor of mammary: a historical perspective. Histopathology 1854, 153(1980):14-25.
• [14]Eisenberg AJ, Hajdus I, Wilhelmus J, Melamed MR, Kinne D: Preoperative aspiration cytology of breast tumors. Acta Cytol 1986, 30:135-146.
• [15]Zatloukal J, Lorenzova J, Tichy F, Nečas A, Kecova H, Kohout P: Breed and age as a risk factors for canine mammary tumours. Acta Vet Brno 2005, 74:103-109.
• [16]Hsu WL, Huang HM, Liao JW, Wong ML, Chang SC: Increased survival in dogs with malignant mammary tumours overexpressing HER-2 protein and detection of a silent single nucleotide polymorphism in the canine HER-2 gene. Vet J 2009, 180:116-123.
• [17]Morris JS, Nixon C, King OJA, Morgan IM, Philbey AW: Expression of TopBP1 in canine mammary neoplasia in relation to histological type, Ki67, ERα and p53. Vet J 2009, 179:422-429.
• [18]Nieto A, Pena L, Perez-alenza MD, Sanchez MA, Flores JM, Castano M: Immunohistologic detection of estrogen receptor alpha in canine mammary tumors: clinical and pathologic associations and prognostic signi fi cance. Vet Pathol 2000, 37:239-247.
• [19]Sarli G, Preziosi C, Benazzi G, Castellani P, Marcato S: Prognostic value of histologic stage and proliferative activity in canine malignant mammary tumors. J Vet Diagn Invest 2002, 14:25-34.
• [20]Yang WY, Liu CH, Chang CJ, Lee CC, Chang KJ, Lin CT: Proliferative activity, apoptosis and expression of oestrogen receptor and Bcl-2 oncoprotein in canine mammary tumours. J Comp Pathol 2006, 134:70-79.
• [21]Karayannopoulou M, Kaldrimidou E, Dessiris A: Some epidemiological aspects of canine mammary tumors treatment and prognosis. Bull. Helen. Vet Med Soc 1989, 40:111-121.
• [22]Fidler IJ, Brodey SR: A necropsy study of canine malign mammary neoplasm. J Am Vet Med Assoc 1967, 151:710-715.
• [23]Pamukcu M, Erturk E: Distribution of tumor types in dogs in Ankara. Vet J Ankara Univ 1962, 9:1-9.
• [24]Choi YD, Choi YH, Lee JH, Nam JH, Juhng SW: Analysis of Fine needle aspiration cytology of the breast. Acta Cytol 2004, 48:801-806.
• [25]Ciatto S, Morrone D, Catarzi S, Del Turco MR, Bianchi S, Ambrogetti D, Cariddi A: Radial scars of the breast: review of 38 consecutive mammographic diagnoses. Radiology 1993, 187(3):757-60.
• [26]Simeonov R, Stoikov D: Study on the correlation between the cytological and histological tests in the diagnostics of canine spontaneous mammary neop-lams. Bulgarian Journal of Veterinary Medicine 2006, 9:211-219.
• [27]Allen SW, Prasse KW, Mahaffey EA: Cytologic differentiation of benign from malignant canine mammary tumors. Vet Pathol 1986, 23:649-655.
• [28]Cassali GD, Gobbi H, Malm C, Schmitt FC: Evaluation of accuracy of fine needle aspiration cytology for diagnosis of canine mammary tumours: Comparative features with human tumours. Cytopathology 2007, 18:191-196.
• [29]Haziroglu R, Yardimci B, Aslan S, Yildirim MZ, Yumusak N, Beceriklisoy H, Agaoglu R, Kucukaslan I: Cytological Evaluation of canine mammary tumours with fine needle aspiration biopsy technique. Revue Méd Vét 2010, 161(5):212-218.
• [30]Misdorp W, Else R, Hellmen E, Lipscomb T: Histologic classification of mammary tumors of the dog and cat. Washington DC: Armed forces institute of pathology; 1999:3-6.
• [31]Sood AK, Seftor EA, Fletcher MS, Gardner LM, Heidger PM, Buller RE, Seftor RE, Hendrix MJ: Molecular determinants of ovarian cancer plasticity. Am J Pathol 2001, 158:1279-1288.
• [32]Shirakawa K, Tsuda H, Heike Y, Kato K, Asada R, Inomata M, Sasaki H, Kasumi F: Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer. Cancer Res 2001, 61:445-451.
• [33]Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe’er J, Trent JM, Meltzer PS, Hendrix MJ: Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 1999, 155:739-752.
• [34]Folberg R, Hendrix MJ, Maniotis AJ: Vasculogenic mimicry and tumor angiogenesis. Am J Pathol 2000, 156:361-381.
• [35]Marconato L, Romanelli G, Stefanello D: Prognostic factors for dogs with mammary inflammatory carcinoma: 43 cases (2003–2008). J Am Vet Assoc 2009, 235:967-972.
• [36]Clemente M, Perez-Alenza MD, Illera JC, Peña L: Histologic, immunologic and ultrastructural description of vasculogenic mimicry in canine mammary cancer. Vet Pathol 2010, 47:265-274.
• [37]De M Souza CH, Toledo-Piza E, Amorin R, Barboza A, Tobias KM: Inflammatory mammary carcinoma in 12 dogs: clinical features, cyclooxygenase-2 expression, and response to piroxicam treatment. Can Vet J 2009, 50(5):506-510.
• [38]Virnig BA, Tuttle TM, Shamliyan T, Kane RL: Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst 2010, 102:170-178.
• [39]Vogl G, Dietze O, Hauser-Kronberger C: Angiogenic potential of ductal carcinoma in situ (DCIS) of human breast. Histopathology 2005, 47:617-624.
• [40]Karayannopoulou M, Kaldrymidou E, Constantinidis TC, Dessiris A: Adjuvant post-operative chemotherapy in bitches with mammary cancer. J Vet Med A 2001, 48:85-96.
• [41]Hampe JF, Misdorp W: Tumours and dysplasias of the mammary gland. B. World. Health. Organ 1974, 50:111-133.
• [42]Gilbertson SR, Kurzman ID, Zachrau RE: Canine mammary epithelial neoplasms: biological implications of morphologic characteristics assessed in 232 dogs. Vet Pathol 1983, 20:127-142.
• [43]Misdorp В, Else R, Hellmen E, Lipscomb T: Histological classification of mammary tumors of the dog and cat. WHO International Histological Classification of Tumors in Domestic Animals. 2nd series, vol. VII. Washington DC: Armed Forces Institute of Pathology, American Registry of Pathology; 2001.
• [44]Tavasoly A, Golshahi H, Rezaie A, Farhadi M: Classification and grading of canine malignant mammary tumors. Veterinary Research Forum 2013, 4(1):25-30.
• [45]Rezaie A, Tavasoli A, Bahonar A, Mehrazma M: Grading in canine mammary gland carcinoma. J Biol Sci 2009, 9:333-338.
• [46]Ežerskytė A, Zamokas G, Grigonis A: The retrospective analysis of mammary tumors in dogs. Vet Med Zoot 2011, 53(75):3-8.
• [47]Rungsipipat A, Tateyama S, Yamaguchi R: Immunohistochemical analysis of c-yes and c-erbB-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors. J Vet Med Sci 1999, 61:27-32.
• [48]Millanta F, Calandrella M, Bari G: Comparison of steroid receptor expression in normal, dysplastic and neoplastic canine and feline mammary tissues. Res Vet Sci 2005, 79:225-232.
• [49]Thuroczy J, Reisvaag GJK, Perge E, Tibold A, Szilagyi J, Balogh L: Immunohistochemical detection of progesterone and cellular proliferation in canine mammary tumours. J Comp Pathol 2007, 137:122-129.
• [50]Misdorp W: Tumors of the mammary gland. In Tumors in Domestic Animals. 4th edition. Edited by Meuten D. Ames, Iowa, USA: Iowa State Press; 2002:575-607.
• [51]Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991, 19:403-410.
• [52]Karayannopoulou M, Kaldrymidou E, Constantinidis TC: Histological grading and prognosis in dogs with mammary carcinomas: application of a human grading method. J Comp Pathol 2005, 133(4):246-252.
• [53]Benjamin SA, Lee AC, Saunders WJ: Classification and behavior of canine mammary epithelial neoplasms based on life-span observations in beagles. Vet Pathol 1999, 36:423-436.
• [54]MacEwen E, Withrow S: Tumors of the mammary gland. In Small Animal Clinical Oncology. 2nd edition. Edited by Withrow S, MacEwen E, Saunders WB. Philadelphia; 1996:pp. 356-372.
• [55]Bibbo M: Comprehensive cytopathology. 2nd edition. Philadelphia: WB Saunders Company; 1997:413-444.
• [56]Rosen PP, Oberman HA: Tumors of mammary gland. In Armed Forces Institute of Pathology. Washington; 1993:p390.