Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-10T17:11:02.616Z Has data issue: false hasContentIssue false
  • English
  • Français

Feline HER2 Protein Expression Levels and Gene Status in Feline Mammary Carcinoma: Optimization of Immunohistochemistry (IHC) and In Situ Hybridization (ISH) Techniques

Published online by Cambridge University Press:  30 May 2013

Maria Soares ,
Jorge Correia ,
Pedro Rodrigues ,
Margarida Simões ,
Alves de Matos  and
Fernando Ferreira
Maria Soares
Affiliation:
CIISA, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Av. da Universidade Técnica, 1300-477 Lisboa, Portugal
Jorge Correia
Affiliation:
CIISA, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Av. da Universidade Técnica, 1300-477 Lisboa, Portugal
Pedro Rodrigues
Affiliation:
Escola Superior de Saúde Egas Moniz, Quinta da Granja, Monte da Caparica, 2829-511 Caparica, Portugal
Margarida Simões
Affiliation:
CIISA, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Av. da Universidade Técnica, 1300-477 Lisboa, Portugal
Alves de Matos
Affiliation:
Escola Superior de Saúde Egas Moniz, Quinta da Granja, Monte da Caparica, 2829-511 Caparica, Portugal Serviço de Anatomia Patológica, Hospital Curry Cabral, Centro Hospitalar de Lisboa Central, R. da Beneficiência, 1069-166 Lisboa, Portugal
Fernando Ferreira*
Affiliation:
CIISA, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Av. da Universidade Técnica, 1300-477 Lisboa, Portugal
*
*Corresponding author. E-mail: fernandof@fmv.utl.pt
Get access

Abstract

Human epidermal growth factor receptor (HER2) is a tumor biomarker that when overexpressed and/or amplified is associated with a poor prognosis for women with breast cancer. This specific tumor subtype is eligible for a specific immunotherapy that increases survival period. However, in feline oncology, only a few studies have been performed on molecular characterization of feline (fHER2) in feline mammary carcinoma (FMC), and the available data are inconsistent. In this study, fHER2 protein levels and gene status in FMC were evaluated by immunohistochemistry and in situ hybridization. After being optimized, these techniques revealed that fHER2 is overexpressed in 33% of FMC cases, although fHER2 and fTOP2A gene amplification could not be observed. Our results support the possibility of using FMC as a natural model for comparative oncology. Additional data obtained may also improve the diagnostics, and consequently the treatment, of this type of tumor in veterinary medicine.

Keywords

feline mammary carcinomas (FMC)feline human epidermal growth factor receptor-2 gene homolog (fHER2)feline topoisomerase 2 alpha gene homolog (fTOP2A)gene amplificationprotein overexpressionimmunohistochemistry (IHC)in situ hybridization (ISH)
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 19 , Issue 4 , August 2013 , pp. 876 - 882
Copyright
Copyright © Microscopy Society of America 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bhargava, R., Lal, P. & Chen, B. (2005). HER-2/neu and topoisomerase II a gene amplification and protein expression in invasive breast carcinomas: Chromogenic in situ hybridization and immunohistochemical analyses. Am J Clin Pathol 123(6), 889–895.Google Scholar
Bilous, M., Dowsett, M., Hanna, W., Isola, J., Lebeau, A., Moreno, A., Penault-Llorca, F., Ruschoff, J., Tomasic, G. & van De Vijver, M. (2003). Current perspectives on HER2 testing: A review of national testing guidelines. Mod Pathol 16(2), 173–182.Google Scholar
Cianciulli, A.M., Botti, C., Coletta, A.M., Buglioni, S., Marzano, R., Benevolo, M., Cione, A. & Mottolese, M. (2002). Contribution of fluorescence in situ hybridization to immunohistochemistry for the evaluation of HER-2 in breast cancer. Cancer Genet Cytogenet 133(1), 66–71.Google Scholar
De Maria, R., Olivero, M., Iussich, S., Nakaichi, M., Murata, T., Biolatti, B. & Di Renzo, M.F. (2005). Spontaneous feline mammary carcinoma is a Model of HER2 overexpressing poor prognosis human breast cancer. Cancer Res 65(3), 907–912.Google Scholar
Elston, C.W. & Ellis, I.O. (1998). Assessment of histological grade. In Rosen's Breast Pathology, Rosen, P.P. (Ed.), pp. 365–382. Philadelphia, PA: Lippincott-Raven.Google Scholar
Fountzilas, G., Valavanis, C., Kotoula, V., Eleftheraki, A.G., Kalogeras, K.T., Tzaida, O., Batistatou, A., Kronenwett, R., Wirtz, R.M., Bobos, M., Timotheadou, E., Soupos, N., Pentheroudakis, G., Gogas, H., Vlachodimitropoulos, D., Polychronidou, G., Aravantinos, G., Koutras, A., Christodoulou, C., Pectasides, D. & Arapantoni, P. (2012). HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy. J Transl Med 10(10), 89–110.Google Scholar
Gancberg, D., Järvinem, T., Di Leo, A., Rouas, G., Cardoso, F., Paesmans, M., Verhest, A., Piccart, M.J., Isola, J. & Larsimont, D. (2002). Evaluation of HER-2/NEU protein expression in breast cancer by immunohistochemistry: An interlaboratory study assessing the reproducibility of HER-2/NEU testing. Breast Cancer Res Treat 74(2), 113–120.Google Scholar
McNeill, C.J., Sorenmo, K.U., Shofer, F.S., Gibeon, L., Durham, A.C., Barber, L.G., Baez, J.L. & Overley, B. (2009). Evaluation of adjuvant doxorubicin-based chemotherapy for the treatment of feline mammary carcinoma. J Vet Intern Med 23(1), 123–129.Google Scholar
Ménard, S., Tagliabue, E., Campiglio, M. & Pupa, S.M. (2000). Role of HER2 gene overexpression in breast carcinoma. J Cell Physiol 182(2), 150–162.Google Scholar
Millanta, F., Calandrella, M., Citi, S., Della Santa, D. & Poli, A. (2005). Overexpression of HER-2 in feline invasive mammary carcinomas: An immunohistochemical survey and evaluation of its prognostic potential. Vet Pathol 42, 30–34.Google Scholar
Misdorp, W., Else, R.W., Hellmen, E. & Lipscomb, T.P. (1999). Histologic classification of mammary tumors of the dog and the cat. In World Health Organization International Histological Classification of Tumours of Domestic Animals, 2nd ed., Schulman, F.Y. (Ed.), vol. 7, pp. 11–27. Washington, DC: Armed Force Institute of Pathology and World Health Organization.Google Scholar
Nassar, A., Cohen, C. & Siddiqui, M. (2009). Estimation of hormone receptor status and HER2 in cytologic cell blocks from breast cancer using the novel rabbit monoclonal antibodies (SP1, SP2, and SP3). Diagn Cytopathol 37(12), 865–870.CrossRefGoogle ScholarPubMed
Oakman, C., Moretti, E., Galardi, F., Santarpia, L. & Di Leo, A. (2009). The role of topoisomerase II alpha and Her-2 in predicting sensitivity to anthracyclines in breast cancer patients. Cancer Treat Rev 35(8), 662–667.Google Scholar
O'Malley, F.P., Parkes, R., Latta, E., Tjan, S., Zadro, T., Mueller, R., Arneson, N., Blackstein, M. & Andrulis, I. (2001). Comparison of HER2/neu status assessed by quantitative polymerase chain reaction and immunohistochemistry. Am J Clin Pathol 115(4), 504–511.CrossRefGoogle ScholarPubMed
Ordás, J., Millán, Y., Dios, R., Reymundo, C. & Martin de las Mula, J. (2007). Proto-oncogene HER-2 in normal, dysplastic and tumorous feline mammary glands: An immunohistochemical and chromogenic in situ hybridization study. BMC Cancer 7, 179.Google Scholar
Porrello, A., Cardelli, P. & Spugnini, E.P. (2004). Pet models in cancer research: General principles. J Exp Clin Cancer Res 23(2), 181–193.Google Scholar
Porrello, A., Cardelli, P. & Spugnini, E.P. (2006). Oncology of companion animals as a model for humans. An overview of tumor histotypes. J Exp Clin Cancer Res 25(1), 97–105.Google Scholar
Rampaul, R.S., Pinder, S.E., Gullick, W.J., Robertson, J.F. & Ellis, I.O. (2002). HER-2 in breast cancer—Methods of detection, clinical significance and future prospects for treatment. Crit Rev Oncol Hematol 43(2), 231–244.CrossRefGoogle ScholarPubMed
Rasotto, R., Caliari, D., Castagnaro, M., Zanetti, R. & Zappulli, V. (2011). An immunohistochemical study of HER-2 expression in feline mammary tumours. J Comp Path 144(2-3), 170–179.Google Scholar
Ricardo, S.A., Milanezi, F., Carvalho, S.T., Leitão, D.R. & Schmitt, F.C. (2007). HER2 evaluation using the novel rabbit monoclonal antibody SP3 and CISH in tissue microarrays of invasive breast carcinomas. J Clin Pathol 60(9), 1001–1005.Google Scholar
Rosa, F.E., Silveira, C.G., Bérgamo, N.A., Neto, F.A., Domingues, M.A., Soares, F.A., Caldeira, J.R. & Rogatto, S.R. (2009). Quantitative real-time RT-PCR and chromogenic in situ hybridization: Precise methods to detect HER-2 status in breast carcinoma. BMC Cancer 23(9), 90.Google Scholar
Santos, S., Bastos, E., Baptista, C.S., Sá, D., Caloustian, C., Guedes-Pinto, H., Gärtner, F., Gut, I.G. & Chaves, R. (2012). Sequence variants and haplotype analysis of cat ERBB2 gene: A survey on spontaneous cat mammary neoplastic and non-neoplastic lesions. Int J Mol Sci 13(3), 2783–2800.Google Scholar
Sidoni, A., Ferri, I., Cavaliere, A., Bellezza, G., Scheibel, M. & Bucciarelli, E. (2006). Detection of HER-2/neu (c-erbB-2) overexpression and amplification in breast carcinomas with ambiguous immunohistochemical results. A further contribution to defining the role of fluorescent in situ hybridization. Anticancer Res 26(3B), 2333–2337.Google Scholar
Sorenmo, K.U., Worley, D.R. & Goldschmidt, M.H. (2013). Tumors of the mammary gland. In Small Animal Clinical Oncology, Withrow, S.J., Vail, D.M. & Page, R.L. (Eds.), pp. 547–552. Philadelphia, PA: Saunders Elsevier.Google Scholar
Stebbing, J., Copson, E. & Reilly, S.O. (2000). Herceptin (trastuzamab) in advanced breast cancer. Cancer Treat Rev 26, 287–290.Google Scholar
Susini, T., Bussani, C., Marini, G., Nori, J., Olivieri, S., Molino, C., Bianchi, S., Vezzosi, V., Paglierani, M., Giachi, M., Borrani, E. & Scarselli, G. (2010). Preoperative assessment of HER-2/neu status in breast carcinoma: The role of quantitative real-time PCR on core-biopsy specimens. Gynecol Oncol 116(2), 234–239.CrossRefGoogle ScholarPubMed
Tanner, M., Isola, J., Wiklund, T., Erikstein, B., Kellokumpu-Lehtinen, P., Malmström, P., Wilking, N., Nilsson, J. & Bergh, J. (2006). Topoisomerase II alpha gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu-amplified breast cancer: Scandinavian Breast Group Trial 9401. J Clin Oncol 24(16), 2428–2436.Google Scholar
Vollan, H.K. & Caldas, C. (2011). The breast cancer genome—A key for better oncology. BMC Cancer 30(11), 501.Google Scholar
Wang, J., Xu, B., Yuan, P., Zhang, P., Li, Q., Ma, F. & Fan, Y. (2012). TOP2A amplification in breast cancer is a predictive marker of anthracycline-based neoadjuvant chemotherapy efficacy. Breast Cancer Res Treat 135(2), 531–537.Google Scholar
Wiston, J., Craft, D.M., Scase, T.J. & Bergman, P.J. (2005). Immunohistochemical detection of HER-2/neu expression in spontaneous feline mammary tumours. Vet Comp Oncol 3(1), 8–15.CrossRefGoogle Scholar
Wolff, A.C., Hammond, M.E., Schwartz, J.N., Hagerty, K.L., Allred, D.C., Cote, R.J., Dowsett, M., Fitzgibbons, P.L., Hanna, W.M., Langer, A., McShane, L.M., Paik, S., Pegram, M.D., Perez, E.A., Press, M.F., Rhodes, A., Sturgeon, C., Taube, S.E., Tubbs, R., Vance, G.H., van de Vijver, M., Wheeler, T.M., Hayes, D.F. & American Society of Clinical Oncology/College of American Pathologists. (2007). American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 131(1), 18–43.Google Scholar