c-erb B2 ve UGCG Köpeklerin Meme Karsinomlarında Güvenilir İmmunohistokimyasal Markerlar mıdır?

Yıl 2021, Cilt: 16 Sayı: 2, 189 - 195, 31.10.2021

Emin Karakurt , Mushap Kuru , Serpil Dağ , Enver Beytut , Hasan Oral , Hilmi Nuhoğlu , Ayfer Yıldız

https://doi.org/10.17094/ataunivbd.840506

Öz

Bu çalışmada, köpek meme tümörlerinde c-erb B2, UGCG ekspresyonları ve tümör boyutu arasında ilişki kurmak amaçlandı. Çalışmanın materyali; 2012-2020 yılları arasında Anabilim Dalımıza getirilen 10 dişi köpekten alınan meme kanseri dokusu örneklerinden oluştu. İmmünohistokimyasal yöntem olarak Avidin-Biotin Peroksidaz yöntemi kullanıldı. Tüm köpek meme tümörü vakaları c-erb B2 ve UGCG reaksiyonları yönünden immun pozitifti. c-erb B2 ve UGCG immun pozitif hücre sayısındaki artışın tümör boyutuna paralel olduğu tespit edildi. Neoplastik epitel hücrelerde membranöz ve sitoplazmik c-erb B2 immün pozitif boyamalar tespit edildi. Reaksiyonların şiddeti orta ila şiddetli düzeydeydi. Neoplastik epitel hücrelerinin sitoplazmasında şiddetli koyu kahverenginde sitoplazmik seramid glukoziltransferaz boyaması tespit edildi. C-erb B2 ve UGCG immün pozitif hücre sayısındaki artışın tümör boyutuna paralel olduğu ortaya konuldu. Sonuç olarak, köpek meme tümörlerinde önemli bir tanı parametresi olan tümör boyutu ile doğru orantılı olarak c-erb B2 ve UGCG pozitif hücre sayısındaki bu artış, bize köpek meme tümörlerinin teşhisinde c-erb B2 ve UGCG'nin güvenilir immunohistokimyasal belirteçler olabileceğini düşündürdü. Ek olarak bu belirteçlerin, farklı kanser tanı parametreleri doğrultusunda kapsamlı bir şekilde değerlendirilmesi elzemdir.

Anahtar Kelimeler

c-erb B2 , köpek , meme tümörü , ugcg

Are c-erb B2 and UGCG Reliable Immunohistochemical Markers Of Canine Mammary Carcinomas?

Öz

In this study, we aimed to correlate c-erb B2, UGCG expressions and tumor size in canine mammary tumors. The material of this study consisted of tissue samples of mammary carcinomas taken from ten female dogs brought to our department between 2012-2020. Avidin-Biotin Peroxidase method was used as an immunohistochemical method. All canine mammary tumor cases were immune positive for c-erb B2 and UGCG reactions. We detected membranous and cytoplasmic c-erb B2 immune positive staining in the neoplastic epithelial cells. Reactions were moderate to strong in severity. We observed strong dark brown cytoplasmic ceramide glucosyltransferase staining in the cytoplasm of neoplastic epithelial cells. We found that the increase in the number of c-erb B2 and UGCG immune positive cells paralleled the tumor size. In conclusion, the increase in the number of c-erb B2 and UGCG positive cells in direct proportion to the tumor size, which is an important diagnostic parameter in canine mammary tumors, made us think that c-erb B2 and UGCG could be reliable immunohistochemical markers in the diagnosis of canine mammary tumors. In addition, these markers must be evaluated comprehensively in line with different cancer diagnosis parameters.

Anahtar Kelimeler

canine , c-erb B2 , mammary tumor , ugcg

Kaynakça

• 1. Muniappan N., Ramesh S., Hemalatha S., Shafiuzama M., Preetha SP., 2019. Expression of biomarkers in canine mammary tumours. Int J Curr Microbiol App Sci, 8, 1464-1473.
• 2. Kaszak I., Ruszczak A., Kanafa S., Kacprzak K., Krol M., Jurka P., 2018. Current biomarkers of canine mammary tumors. Acta Vet Scand, 60, 66.
• 3. Mouser P., Miller MA., Antuofermo E., Badve SS., Mohammed SI., 2010. Prevalence and classification of spontaneous mammary intraepithelial lesions in dogs without clinical mammary disease. Vet Pathol, 47, 275-284.
• 4. Varallo GR., Gelaleti GB., Maschio-Signorini LB., Moschetta MG., Lopes JR., De Nardi AB., Tinucci- Costa M., Rocha RM., De Campos Zuccari DAP., 2019. Prognostic phenotypic classification for canine mammary tumors. Oncol Lett, 18, 6545- 6553.
• 5. Gama A., Alves A., Schmitt F., 2008. Identification of molecular phenotypes in canine mammary carcinomas with clinical implications: application of the human classification. Virchows Arch, 453, 123-132.
• 6. Araujo MR., Campos LC., Damasceno KA., Gamba CO., Ferreira E., Cassali GD., 2016. HER-2, EGFR, Cox-2 and Ki67 expression in lymph node metastasis of canine mammary carcinomas: Association with clinical-pathological parameters and overall survival. Res Vet Sci, 106, 121-130.
• 7. Ressel L., Puleio R., Loria GR., Vannozzi I., Millanta F., Caracappa S., Poli A., 2013. HER-2 expression in canine morphologically normal, hyperplastic and neoplastic mammary tissues and its correlation with the clinical outcome. Res Vet Sci, 94, 299-305.
• 8. Martin de las Mulas J., Ordas J., Millan Y., Fernandez-Soria V., Ramon y Cajal S., 2003. Oncogene HER-2 in canine mammary gland carcinomas: an immunohistochemical and chromogenic in situ hybridization study. Breast Cancer Res Treat, 80, 363-367.
• 9. Hsu WL., Huang HM., Liao JW., Wong ML., Chang SC., 2009. 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, 180, 116-123.
• 10. Kim JH., Im KS., Kim NH., Yhee JY., Nho WG., Sur JH., 2011. Expression of HER-2 and nuclear localization of HER-3 protein in canine mammary tumors: histopathological and immunohistochemical study. Vet J, 189, 318-322.
• 11. Muhammadnejad A., Keyhani E., Mortazavi P., Behjati F., Haghdoost IS., 2012. Overexpression of her-2/neu in malignant mammary tumors; translation of clinicopathological features from dog to human. Asian Pac J Cancer Prev, 13, 6415-6421.
• 12. Rungsipipat A., Tangkawatana S., Sailasuta A., Lohachit C., Chariyalertsak S., 2008. C-erbB-2 oncogene and P21WAF/CIP1 tumor suppressor gene expression as prognostic factors in canine mammary adenocarcinomas. Comp Clin Pathol, 17, 35-41.
• 13. Queiroga FL., Raposo T., Carvalho MI., Prada J., Pires I., 2011. Canine mammary tumours as a model to study human breast cancer: most recent findings. In Vivo, 25, 455-466.
• 14. Bertagnolli AC., Ferreira E., Dias EJ., Cassali GD., 2011. Canine mammary mixed tumours: immunohistochemical expressions of EGFR and HER-2. Aust Vet J, 89, 312-317.
• 15. Pena L., Gama A., Goldschmidt MH., Abadie J., Benazzi C., Castagnaro M., Diez L., Gartner F., Hellmen E., Kiupel M., Millan Y., Miller MA., Nguyen F., Poli A., Sarli G., Zappulli V., de las Mulas JM., 2014. Canine mammary tumors: a review and consensus of standard guidelines on epithelial and myoepithelial phenotype markers, HER2, and hormone receptor assessment using immunohistochemistry. Vet Pathol, 51, 127-145.
• 16. Che J., Huang Y., Xu C., Zhang P., 2017. Increased ceramide production sensitizes breast cancer cell response to chemotherapy. Cancer Chemother Pharmacol, 79, 933-941.
• 17. Wegner MS., Schömel N., Gruber L., Örtel SB., Kjellberg MA., Mattjus P., Kurz J., Trautmann S., Peng B., Wegner M., Kaulich M., Ahrends R., Geisslinger G., Grösch S., 2018. UDP-glucose ceramide glucosyltransferase activates AKT, promoted proliferation, and doxorubicin resistance in breast cancer cells. Cell Mol Life Sci, 75, 3393-3410.
• 18. Schömel N., Hancock SE., Gruber L., Olzomer EM., Byrne FL., Shah D., Hoehn KL., Turner N., Grösch S., Geisslinger G., Wegner MS., 2019. UGCG influences glutamine metabolism of breast cancer cells. Sci Rep, 9, 15665.
• 19. Schömel N., Gruber L., Alexopoulos SJ., Trautmann S., Olzomer EM., Byrne FL., Hoehn KL., Gurke R., Thomas D., Ferreiros N., Geisslinger G., Wegner MS., 2020. UGCG overexpression leads to increased glycolysis and increased oxidative phosphorylation of breast cancer cells. Sci Rep, 10, 8182.
• 20. Al-Mansour MA., Kubba MAG., Al-Azreg SA., Dribika SA., 2018. Comparative histopathology and immunohistochemistry of human and canine mammary tumors. Open Vet J, 8, 243- 249.
• 21. Dutra AP., Granja NV., Schmitt FC., Cassali GD., 2004. c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors. Braz J Med Biol Res, 37, 1673-1681.
• 22. Rungsipipat A., Tateyama S., Yamaguchi R., Uchida K., Miyoshi N., Hayashi T., 1999. Immunohistochemical analysis of c-yes and cerbB-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors. J Vet Med Sci, 61, 27-32.
• 23. Winston J., Craft DM., Scase TJ., Bergman PJ., 2005. Immunohistochemical detection of HER- 2/neu expression in spontaneous feline mammary tumours. Vet Comp Oncol, 3, 8-15.
• 24. Rezaie A., Tavasoli A., Mehrazma M., Bahonar A., 2012. c-erbB2 receptor and P53 protein expression in canine mammary gland carcinoma. Comp Clin Pathol, 21, 1633-1636.
• 25. Pedraza-Ordonez F., Montoya-Florez LM., Bulla C., Rocha NS., 2015. Analisys of immunohistochemical prognostic markers in canine mammary cancer and its relation to postsurgical survival. OJ Pathology, 5, 90-99.
• 26. Singer J., Weichselbaumer M., Stockner T., Mechtcheriakova D., Sobanov Y., Bajna E., Wrba F., Horvat R., Thalhammer JG., Willmann M., Jensen-Jarolim E., 2012. Comparative oncology: ErbB-1 and ErbB-2 homologues in canine cancer are susceptible to cetuximab and trastuzumab targeting. Mol Immunol, 50, 200-209.
• 27. Muscatello LV., Sarli G., Beha G., Asproni P., Millanta F., Poli A., De Tolla LJ., Benazzi C., Brunetti B., 2015. Validation of tissue microarray for molecular profiling of canine and feline mammary tumours. J Comp Pathol, 152, 153-160.
• 28. Klopfleisch R., Klose P., Weise C., Bondzio A., Multhaup G., Einspanier R., Gruber AD., 2010. Proteome of metastatic canine mammary carcinomas: similarities to and differences from human breast cancer. J Proteome Res, 9, 6380-6391.
• 29. Seung BJ., Cho SH., Kim SH., Lim HY., Sur JH., 2020. Quantitative analysis of HER2 mRNA expression by RNA in situ hybridization in canine mammary gland tumors: Comparison with immunohistochemistry analysis. PLoS One, 15, e0229031.