DOI QR코드

DOI QR Code

Overexpression of HER-2/neu in Malignant Mammary Tumors: Translation of Clinicopathological Features from Dog to Human

  • Muhammadnejad, Ahad (Department of Pathology, Faculty of Specialized Veterinary Sciences, Science Research Branch, Islamic Azad University) ;
  • Keyhani, Elahe (Genetics Research Center, University of Social Welfare and Rehabilitation Sciences) ;
  • Mortazavi, Pejman (Department of Pathology, Faculty of Specialized Veterinary Sciences, Science Research Branch, Islamic Azad University) ;
  • Behjati, Farkhondeh (Genetics Research Center, University of Social Welfare and Rehabilitation Sciences) ;
  • Haghdoost, Iraj Sohrabi (Department of Pathology, Faculty of Specialized Veterinary Sciences, Science Research Branch, Islamic Azad University)
  • Published : 2012.12.31

Abstract

Background: Canine mammary gland tumors (CMGTs) are the most common tumor found in bitches. Changes in HER-2/neu genes in human breast cancer (HBC) lead to decrease in disease-free survival (DFS) and overall survival rate (OSR). Previous studies have demonstrated that the biological behavior of malignant mammary gland tumors (MMGTs) is similar to that of HBC. The present study aimed at evaluating the relationship between overexpression of HER-2/neu and clinicopathological features in MMGTs to represent a model of prognostic factors for HBC. Materials and Method: The clinicopathological data of 35 MMGTs were obtained. Immunohistochemical staining with HER-2, Ki-67 and CD34 markers was conducted with sections from paraffin-embedded blocks. According to standard protocols, histological type, grade, margin status, lymphovascular invasion (LVI), HER-2/neu score, proliferation rate and microvessel density (MVD) of tumors were determined and the association of HER-2/neu overexpression with these parameters was assessed statistically. Results: The IHC results showed that 12 (34.3%) cases were HER-2/neu positive. Statistical analyses indicated a significant relationship between HER-2 positivity and tumor grade (p=0.043), which also was demonstrated with cancer stage (p=0.035), tumor margin involvement (p=0.016), proliferation index (p=0.001) and MVD (p=0.001); however, there was no statistical relationship between LVI and tumor size. Overexpression of the HER-2/neu gene in MMGTs results in similar biological behavior as that of HBC; as a result, these tumors have can be considered to have important similarities in clinicopathological characteristics. Conclusions: MMGTs can be regarded as an HBC animal model. Further studies in this field would result in new treatments that could be beneficial for both dogs and humans.

Keywords

References

  1. Akhdar A, Bronsard M, Lemieux R, Geha S (2011). HER-2 oncogene amplification assessment in invasive breast cancer by dual-color in situ hybridization (dc-CISH): a comparative study with fluorescent in situ hybridization (FISH). Ann Pathol, 31, 472-9. https://doi.org/10.1016/j.annpat.2011.10.013
  2. Aksu G, Dumn C, Gurbuz Y, et al (2011). Correlation between c-erbB2 expression, lymphovascular invasion and other biological and clinical prognostic factors and preoperative tumor markers in patients with early-stage and locally advanced breast cancer. J BUON, 16, 52-7.
  3. Andrade FH, Figueiroa FC, Bersacot DZ, Rocha NS (2010). Malignant mammary tumor in female dogs: environmental contaminants. Diagn Pathol, 5, 45. https://doi.org/10.1186/1746-1596-5-45
  4. Angelica CB, Alessandra Estrela-Lima, (2011). Consensus for the Diagnosis, Prognosis and Treatment of Canine Mammary Tumors. Braz J Vet Pathol, 4, 153-80.
  5. Antuofermo E, Miller MA, Pirino S, et al (2007). Spontaneous mammary intraepithelial lesions in dogs-a model of breast cancer. Cancer Epidemiol Biomarkers Prev, 16, 2247-56. https://doi.org/10.1158/1055-9965.EPI-06-0932
  6. Azizun-Nisa, Bhurgri Y, Reza F, Kayani N (2008). Comparison of ER, PR and HER-2/neu (C-erb B 2) reactivity pattern with histologic grade, tumor size and lymph node status in breast cancer. Asian Pac J Cancer Prev, 9, 553-6.
  7. Baqaria SP, Ray PS, Wang J, et al (2012). Prognostic value of basal phenotype in HER-2-overexpressing breast cancer. Ann Surg Oncol, 19, 935-40. https://doi.org/10.1245/s10434-011-2032-5
  8. Baquet CR, Mishra SI, Commiskey P, Ellison GL, DeShields M (2008). Breast cancer epidemiology in blacks and whites: disparities in incidence, mortality, survival rates and histology. J Natl Med Assoc, 100, 480-8.
  9. Burestein HJ, Winer EP (2009). Refining therapy for human epidermal growth factor receptor 2-positive breast cancer: T stands for trastuzumab, tumor size, and treatment strategy. J Clin Oncol, 27, 5671-3. https://doi.org/10.1200/JCO.2009.24.2222
  10. Chen ST, Lai HW, Tseng HS, et al (2011). Correlation of histologic grade with other clinicopathological parameters, intrinsic subtype, and patients' clinical outcome in Taiwanese women. Jpn J Clin Oncol, 41, 1327-35. https://doi.org/10.1093/jjco/hyr157
  11. Chu PY, Hsu NC, Liao AT, et al (2011). Overexpression of ${\alpha}$-enolase correlates with poor survival in canine mammary carcinoma. BMC Vet Res, 7, 62. https://doi.org/10.1186/1746-6148-7-62
  12. Cintra JR, Teixeira MT, Diniz RW, et al (2012). Immunohistochemical profile and clinical-pathological variables in breast cancer. Rev Assoc Med Bras, 58, 178-87.
  13. Dhakal HP, Bassaova A, Naume B, et al (2009). Breast carcinoma vascularity: a comparison of manual microvessel count and Chalkley count. Histol Histopathol, 24, 1049-59.
  14. Dicken BJ, Graham K, Hamilton SM, et al (2006). Lymphovascular invasion is associated with poor survival in gastric cancer. Ann Surg, 243, 64-73. https://doi.org/10.1097/01.sla.0000194087.96582.3e
  15. Dunne C, Burke JP, Morrow M, Kell MR (2009). Effect of margin status on local recurrence after breast conservation and radiation therapy for ductal carcinoma in situ. J Clin Oncol, 27, 1615-20. https://doi.org/10.1200/JCO.2008.17.5182
  16. Ejlertsen B, Jensen MB, Rank F, et al (2009). Population-based study of peritumoral lymphovascular invasion and outcome among patients with operable breast cancer. J Natl Cancer Inst, 101, 729-35. https://doi.org/10.1093/jnci/djp090
  17. Gama A, Alves A, Schmott F (2008). Identification of molecular phenotypes in canine mammary carcinomas with clinical implications: application of the human classification. Virchowe Arch, 453, 123-32. https://doi.org/10.1007/s00428-008-0644-3
  18. Geovanni DC, Gleidice EL, Andrigo BDe Nardi, et al (2009). Comparison of three vascular endothelial markers in the evaluation of microvessel density in breast cancer. Eur J Gynaecol Oncol, 30, 285-8.
  19. Goldherish A, Wood WC, Coates AS, et al (2011). Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. gallen international expert consensus on the primary therapy of early breast Cancer. Ann Oncol, 22, 736-47.
  20. Goldschmidt M, Pena L, Rasotto R, Zappulli V (2011). Classification and grading of canine mammary tumors. Vet Patho, 48, 117-31. https://doi.org/10.1177/0300985810393258
  21. Hasiwa N, Bailery J, Clausing P, et al (2011). Critical evaluation of the use of dogs in biomedical research and testing in Europe. ALTEX, 28, 326-40. https://doi.org/10.14573/altex.2011.4.326
  22. Hus WL, Huang HM, Liao JW, Wong ML, Chang SC (2009). Increased survival in dogs with malignant mammary tumors overexpressing HER-2 protein and detection of a silent single nucleotide polymorphism in the canine HER-2 gene. Vet J, 180, 116-23. https://doi.org/10.1016/j.tvjl.2007.10.013
  23. Itoh T, Uchida K, Ishikawa K, et al (2005). Clinicopathological survey of 101 canine mammary gland tumors: differences between small-breed dogs and others. J Vet Med Sci, 67, 345-7. https://doi.org/10.1292/jvms.67.345
  24. Jamal A, Ward E, Thun MJ (2007). Recent trends in breast cancer incidence rates by age and tumor characteristics among U.S. women. Breast Cancer Res, 9, 28. https://doi.org/10.1186/bcr1672
  25. Jones RL, Salter J, A'Hern R, et al (2009). The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat, 116, 53-68. https://doi.org/10.1007/s10549-008-0081-7
  26. Karyannopoulo M, Kaldrymidou E, Constainidis TC, Dessiris A (2005). Histological grading and prognosis in dogs with mammary carcinomas: application of a human grading method. J Com Pathol, 133, 246-52. https://doi.org/10.1016/j.jcpa.2005.05.003
  27. Kebel RS (2008). Tumor Angiogenesis. N Engl J Med, 358, 19. https://doi.org/10.1056/NEJMicm070903
  28. Khoruzhenko A, KuKHarchuk V, Cherednyk O, et al (2010). Monoclonal antibodies to Ki-67 protein suitable for immunohistochemical analysis. Hybridoma (Lachmt), 29, 301-4. https://doi.org/10.1089/hyb.2009.0118
  29. Klopfleisch R, von Euler H, Sarli G, et al (2011). Molecular carcinogenesis of canine mammary tumors: news from an old disease. Vet Pathol, 48, 98-116. https://doi.org/10.1177/0300985810390826
  30. Lorenza J, Crha M, Kecova H, et al (2010). Patient survival periods and death causes following surgical treatment of mammary gland tumors depending on histological type of tumor: retrospective study of 221 cases. ACTA VET, 79, 289-97. https://doi.org/10.2754/avb201079020289
  31. Metzger FL (2005). Senior and geriatric care programs for veterinarians. Vet Clin North Am Small Pract, 35, 743-53. https://doi.org/10.1016/j.cvsm.2004.12.005
  32. Miglietta L, Vanella P, Canobbio L, et al (2009). Clinical and pathological response to primary chemotherapy in patients with locally advanced breast cancer grouped according to hormonal receptors, HER-2 status, grading and Ki-67 proliferation index. Anticancer Res, 29, 1621-5.
  33. Mohammed RA, Martin SG, Gill MS, et al (2007). Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences. Am J Surg Pathol, 31, 1825-33. https://doi.org/10.1097/PAS.0b013e31806841f6
  34. Nieto Y, Woods J, Nawaz F, et al (2007). Prognostic analysis of tumour angiogenesis, determined by microvessel density and expression of vascular endothelial growth factor, in highrisk primary breast cancer patients treated with high-dose chemotherapy. Br J Cancer, 97, 391-7. https://doi.org/10.1038/sj.bjc.6603875
  35. Park S, Park HS, Koo JS, et al (2012). Breast cancers presenting luminal B subtype features show higher discordant human epidermal growth factor receptor 2 results between immunohistochemistry and fluorescence in situ hybridization. Cancer, 118, 914-23. https://doi.org/10.1002/cncr.26406
  36. Philbert JC, Synder PW, Glickman N, et al (2003). Influence of host factors on survival in dogs with malignant mammary gland tumors. J Vet Internal Med, 17, 102-6. https://doi.org/10.1111/j.1939-1676.2003.tb01330.x
  37. Pinho SS, Cavalho S, Carbral J, Reis CA, Gartner F (2012). Canine tumors: a spontaneous animal model of human carcinogenesis. Transl Res, 159, 165-72. https://doi.org/10.1016/j.trsl.2011.11.005
  38. Queiroga FL, Raposo T, Caravalho MI, Parada J, Pires I (2011) Canine mammary tumours as a model to study human breast cancer: most recent findings. In Vivo, 25, 455-65.
  39. Ragage F, Debled M, MacGrogan G, et al (2010). Is it useful to detect lymphovascular invasion in lymph node-positive patients with primary operable breast cancer? Cancer, 116, 3093-101. https://doi.org/10.1002/cncr.25137
  40. Rakovitch E, Nofech-Mozes S, Hanna W, et al (2012). HER-2/ neu and Ki-67 expression predict non-invasive recurrence following breast-conserving therapy for ductal carcinoma in situ. Br J Cancer, 106, 1160-5. https://doi.org/10.1038/bjc.2012.41
  41. Ramadan SS, Yapicier O, Kihtir S, et al (2011). Correlation of HER 2/neu gene amplification with immunohistochemistry and other prognostic factors in breast carcinoma. Turk Patoloji Derg, 27, 196-203.
  42. Ryska A, Hovorkova E, Rozkos T, Laco J (2011). Predictive diagnosis of breast cancer. Cesk patol, 47, 145-7.
  43. Sassi F, Benazii C, Castellani G, Sarli G (2010). Molecular-based tumour subtypes of canine mammary carcinomas assessed by immunohistochemistry. BMC Vet, 6, 5. https://doi.org/10.1186/1746-6148-6-5
  44. Schoppmann SF, Tamadl D, Roberts L, Jomrich G, Schoppmann A, Zwrtek R, et al. 2010. HER-2/neu expression correlates with vascular endothelial growth factor-C and lymphangiogenesis in lymph node-positive breast cancer. Ann Oncol, 21(5):955-60 https://doi.org/10.1093/annonc/mdp532
  45. Simon D, Schoenrock D, Baumgartner W, Nolte I (2006). Postoperative adjuvant treatment of invasive malignant mammary gland tumors in dogs with doxorubicin and docetaxel. J Vet Intern Med, 20, 1184-90.
  46. Slamon D, Eiermann W, Robert N, et al (2011). The new englandjournal of medicine. N Engl J Med, 365, 14. https://doi.org/10.1056/NEJMicm1012468
  47. Tortora G (2011). Mechanisms of resistance to HER-2 target therapy. J Natl Cancer Inst Monogr, 43, 95-8.
  48. Uzzan B, Ninolas P, Cucherat M, Perret GY (2004). Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res, 64, 2941-55. https://doi.org/10.1158/0008-5472.CAN-03-1957
  49. Vamesu S (2007). Angiogenesis and c-erbB-2 (HER-2/neu) overexpression status in primary breast cancer patients: an analysis of 158 needle core biopsies. Rom J Morphol Embryol, 48, 121-9.
  50. Vogel CL (2012). Dual HER-2-targeted approaches in HER-2-positive breast cancer. Breast Cancer Res Treat, 131, 371-83. https://doi.org/10.1007/s10549-011-1781-y
  51. Wolff AC, Hammond ME, Schwartz JN, et al (2007). American society of clinical oncology/college of american pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol, 25, 118-45.
  52. Workman P, Aboagye EO, Balkwill F, et al (2010). Guidelines for the welfare and use of animals in cancer research. Br J Cancer, 102, 1555-77. https://doi.org/10.1038/sj.bjc.6605642
  53. Young RJ, Reed MW (2012). Anti-angiogenic therapy: concept to clinic. Microcirculation, 19, 115-25 https://doi.org/10.1111/j.1549-8719.2011.00147.x

Cited by

  1. Expression of vimentin filaments in canine malignant mammary gland tumors: A simulation of clinicopathological features of human breast cancer vol.2, pp.5, 2014, https://doi.org/10.3892/br.2014.312
  2. Analisys of Immunohistochemical Prognostic Markers in Canine Mammary Cancer and Its Relation to Postsurgical Survival vol.05, pp.03, 2015, https://doi.org/10.4236/ojpathology.2015.53013
  3. Investigation of HER2 expression in canine mammary tumors by antibody-based, transcriptomic and mass spectrometry analysis: is the dog a suitable animal model for human breast cancer? vol.36, pp.11, 2015, https://doi.org/10.1007/s13277-015-3661-2
  4. Overexpression of HER-2 via immunohistochemistry in canine urinary bladder transitional cell carcinoma - A marker of malignancy and possible therapeutic target pp.14765810, 2017, https://doi.org/10.1111/vco.12345
  5. Canine invasive mammary carcinomas as models of human breast cancer. Part 1: natural history and prognostic factors pp.1573-7217, 2018, https://doi.org/10.1007/s10549-017-4548-2
  6. Why man's best friend, the dog, could also benefit from an anti-HER-2 vaccine vol.12, pp.4, 2016, https://doi.org/10.3892/ol.2016.5001
  7. Current biomarkers of canine mammary tumors vol.60, pp.1, 2018, https://doi.org/10.1186/s13028-018-0417-1