Infiltrating inflammatory cells: Profile and distribution in feline mammary carcinomas

Authors

DOI:

https://doi.org/10.33448/rsd-v10i3.13651

Keywords:

Feline; Inflammatory infiltrate; Lymphocyte; Mammary tumor.

Abstract

Malignant mammary tumors have a relatively high number of infiltrating T lymphocytes. Currently, B lymphocytes infiltrated in tumors have been recognized as a potential marker in human breast cancer. The aim of this study was to relate prognostic factors of mammary tumors to the pattern of inflammatory infiltrate in cats. Protocols of 38 animals diagnosed with mammary tumor were analyzed and data on sex, age and race were obtained. The samples were evaluated for distribution, histological type, size, histological grade, lymph node metastasis, inflammatory cell distribution and intensity of inflammation. For immunohistochemical staining, anti-CD79a monoclonal antibody was used. There was a predominance of elderly and mixed breed cats. Tubular, solid and cribriform carcinomas were the most diagnosed. Grade III tumors smaller than 2.0 cm were frequent. The total inflammatory infiltrate was predominantly multifocal and of low count, regardless of the histological type, degree and size. Lymphocytes were the most frequent and low-count cells. CD79a immunostaining was observed in most neoplasms, showing that B lymphocytes and plasma cells are integral components of the inflammatory infiltrate of the tumor and of predominantly diffuse distribution. Positive CD79a cells showed significant differences in distribution (p = 0.038), in size (p = 0.045) and lymphatic invasion (p = 0.039). This is the first study to quantify inflammatory cells in the mammary tumor microenvironment of cats and reveals promising initial results. CD79a positive cells constitute a significant portion of the lymphocyte population in the tumor microenvironment and are part of the tumor-associated inflammatory response in feline breast carcinomas.

Author Biographies

Michele Berselli, Universidade de Santa Cruz do Sul

Graduated in Veterinary Medicine from the Federal University of Pelotas (2007). Specialist in Small Animal Medical Clinic - Residence I (2008) at Hospital de Clínicas Veterinária, Universidade Federal de Pelotas (2008). Master of Science, from the Veterinary Graduate Program, in the Animal Pathology area - UFPel (2011). He has experience in the area of ​​Veterinary Medicine, with an emphasis on Clinical Medicine and Animal Pathology working on the following themes: animal pathology, pathologies of companion animals, oncology, breast neoplasms and immunohistochemistry. She was an assistant professor in the veterinary medicine course at Unicruz, in the disciplines of general pathology and histology, as well as being responsible for the routine of the animal pathology laboratory (histotechnics). She served as a professor in the veterinary medicine course at Unoesc, in the disciplines of histology I, histology II and immunology, small animal semiology and general pathology. PhD student by the postgraduate program in Veterinary Medicine in the area of ​​animal pathology at UFPel and member of the service of veterinary oncology (SOVET) in 2016-2019. Currently professor of the Veterinary Medicine course at UNISC.

Thomas Normanton Guim, Federal University of Pelotas

Graduated from the Federal University of Pelotas (UFPel), holds a Master's and Doctorate in Veterinary Sciences (Animal Pathology) from UFPel, with an emphasis on Veterinary Oncology and a Master's Degree in Animal Science from the Federal University of Pampa in the area of ​​Veterinary Anesthesiology. He worked as a professor in the disciplines of Hospital Practice and Clinical Surgery (Anesthesiology) for three years at UFPel (2003-2005 and 2008 respectively). He is currently a Veterinary Doctor at UFPel and works at the Hospital de Clínicas Veterinária. He is one of the coordinators of the Veterinary Oncology Service (SOVET-UFPel) and works in the routine of the Veterinary Anesthesiology Service at UFPel. He is a member of the Brazilian College of Veterinary Anesthesiology. He has experience in the area of ​​Veterinary Medicine, with an emphasis on Anesthesiology, Veterinary Clinic and Animal Pathology, acting mainly on the following themes: companion animals, oncology, surgical pathology, breast neoplasms, cancer prognostic factors, anesthesiology, anesthesia and analgesia of the patient with cancer.

Clarissa Caetano de Castro, Federal University of Pelotas

Graduated in Veterinary Medicine from the Federal University of Pelotas (2008), Master of Science in Preventive Veterinary from the Federal University of Pelotas (2011) and PhD in Sciences in the area of Animal Health from the Federal University of Pelotas (2016). He is currently doing post-doctorate (PNPD - Capes) at the Federal University of Pelotas. He has experience in the areas of Small Animal Medical Clinic and Preventive Veterinary Medicine, with an emphasis on viral infectious diseases.

Luísa Grecco Corrêa, Federal University of Pelotas

Veterinary Physician graduated from the Federal University of Pelotas - UFPel (2018). She holds a Master's Degree in Animal Health from the Veterinary Graduate Program-PPGV / UFPel (2021). Collaborator of the Veterinary Oncology Service - SOVET UFPel. She has experience in small animal medical clinic and animal pathology with an emphasis on veterinary oncology. She is currently a doctoral student at the Veterinary Graduate Program - PPGV / UFPel.

Andressa Dutra Piovesan Rossato, Institute of Educational Development of Alto Uruguay

Graduated in Veterinary Medicine from the University of Cruz Alta (2014), specialization in Medical and Surgical Clinic of Small Animals from the Qualittas Institute (2016) and Master's Degree (2016) from the Postgraduate Program in Veterinary Medicine (Animal Pathology Area), from the Federal University of Pelotas (PPGV-UFPEL). She is currently Professor of the Veterinary Medicine Course at the Instituto de Desenvolvimento Educacional do Alto Uruguay campus Bagé (IDEAU), in the disciplines of Biological Processes I and Veterinary Pathology. She is currently a PhD student in the Postgraduate Program in Veterinary Medicine at the Federal University of Pelotas in the area of Animal Pathology.

Luísa Mariano Cerqueira da Silva, Federal University of Pelotas

Veterinary Physician graduated from the Federal University of Pelotas in 2014. Master's degree with emphasis on Animal Pathology (2017) and doctoral student at PPGV at UFPEL, emphasis on Animal Reproduction and Animal Pathology.

Fabiane Borelli Grecco, Federal University of Pelotas

Professor of Pathology at the Veterinary Faculty of UFPEL. She has experience in pathology of small animals working mainly on the following topics: animal pathology, oncology and histopathology of renal and hepatic lesions in dogs and cats, and teaching in higher education. PhD in Veterinary Sciences (2009). She is currently a collaborating pathologist at the Veterinary Oncology Service (SOVET) at the Veterinary Faculty of UFPEL.

Fabio Raphael Pascoti Bruhn, Federal University of Pelotas

Adjunct professor at the Federal University of Pelotas (UFPel), linked to the Preventive Veterinary Department of the Faculty of Veterinary Medicine. Professor of the veterinary graduate program and the microbiology and parasitology graduate program at UFPel. Graduated in veterinary medicine and doctor in veterinary sciences, in the area of Collective Health and Animal Health from the Federal University of Lavras (UFLA). He works mainly in the field of epidemiology applied to public, animal and environmental health.

Cristina Gevehr Fernandes, Federal University of Pelotas

Graduated in Veterinary Medicine from the Federal University of Santa Maria (1990), Master in Veterinary Medicine from the Federal University of Santa Maria (1995) and doctorate in Pathology from the Universidade Estadual Paulista Júlio de Mesquita Filho (2001). She is currently a Full Professor at the Federal University of Pelotas. Specialist in Veterinary Pathology by ABPV. She works in teaching, research and extension. She is the coordinator of an extension project called "Veterinary Oncology Service-Pathology / UFPel (SOVET-Pathology / UFPel)" where she performs an anatomo-pathological diagnosis. She has experience in the field of Veterinary pathology, highlighting the following themes: oncology, pathology , histopathology, immunopathology.

References

Borrego, J. F., Cartagena, J. C., & Engel, J. (2009). Treatment of feline mammary tumours using chemotherapy, surgery and a COX-2 inhibitor drug (meloxicam): A retrospective study of 23 cases (2002-2007). Veterinary and Comparative Oncology, 7(4), 213–221. 10.1111/j.1476-5829.2009.00194.x.

Campos, C. B., Damasceno, K. A., Gamba, C. O., Ribeiro, A. M., Machado, C. J., Lavalle, G. E., & Cassali, G. D. (2016). Evaluation of prognostic factors and survival rates in malignant feline mammary gland neoplasms. Journal of Feline Medicine and Surgery, 18(12), 1003–1012. 10.1177/1098612X15610367.

Carvalho, M. I., Pires, I., Prada, J., & Queiroga, F. L. (2011). T-lymphocytic infiltrate in canine mammary tumours: Clinic and prognostic implications. In Vivo, 25(6), 963–969.

Carvalho, M. I., Silva-Carvalho, R., Pires, I., Prada, J., Bianchini, R., Jensen-Jarolim, E., & Queiroga, F. L. (2016). A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs. BioMed Research International, 2016. 10.1155/2016/4917387.

Cassali, G. D., Campos, C. B., Bertagnolli, A. C., Lima, A. E., Lavalle, G. E., Damasceno, K. A., Nardi, A. B. de;, Cogliati, B., Costa, F. V. A. da;, Sobral, R., Di Santis, G. W., Fernandes, C. G., Ferreira, E., Salgado, B. S., Vieira Filho, C. H. C., Silva, D. N., Martins Filho, E. F., Teixeira, S. V., Nunes, F. C., & Nakagaki, K. Y. R. (2018). Consensus for the diagnosis, prognosis and treatment of feline mammary tumors. Brazilian Journal of Veterinary Research and Animal Science, 55(2), 1–17. 10.11606/issn.1678-4456.bjvras.2018.135084.

Cassali, G. D., Jark, P., Gamba, C., Damasceno, K., Estrela-Lima, A., Nardi, A. B., Ferreira, E., Horta, R., Firmo, B., Sueiro, F., Rodrigues, L., & Nakagaki, K. (2020). Consensus Regarding the Diagnosis, Prognosis and Treatment of Canine and Feline Mammary Tumors - 2019. Brazilian Journal of Veterinary Pathology, 13(3), 555–574. 10.24070/bjvp.1983-0246.v13i3p555-574.

Dagher, E., Abadie, J., Loussouarn, D., Campone, M., & Nguyen, F. (2019). Feline Invasive Mammary Carcinomas: Prognostic Value of Histological Grading. Veterinary Pathology, 56(5), 660–670. 10.1177/0300985819846870.

De Souza, T. A., de Campos, C. B., De Biasi Bassani Gonçalves, A., Nunes, F. C., Monteiro, L. N., de Oliveira Vasconcelos, R., & Cassali, G. D. (2018). Relationship between the inflammatory tumor microenvironment and different histologic types of canine mammary tumors. Research in Veterinary Science, 119(October 2017), 209–214. 10.1016/j.rvsc.2018.06.012.

Elston, C. W., & Ellis, I. O. (1991). Pathological prognostic factors in breast cancer: experience from a large study with long-term follow-up. Histopathology, 19, 403–410. 10.1111/j.1365-2559.1991.tb00229.x.

Estrela-Lima, A., Araújo, M. S. S., Costa-Neto, J. M., Teixeira-Carvalho, A., Barrouin-Melo, S. M., Cardoso, S. V., Martins-Filho, O. A., Serakides, R., & Cassali, G. D. (2010). Immunophenotypic features of tumor infiltrating lymphocytes from mammary carcinomas in female dogs associated with prognostic factors and survival rates. BMC Cancer, 10. 10.1186/1471-2407-10-256.

Franzoni, M. S., Brandi, A., de Oliveira Matos Prado, J. K., Elias, F., Dalmolin, F., de Faria Lainetti, P., Prado, M. C. M., Leis-Filho, A. F., & Fonseca-Alves, C. E. (2019). Tumor-infiltrating CD4+ and CD8+ lymphocytes and macrophages are associated with prognostic factors in triple-negative canine mammary complex type carcinoma. Research in Veterinary Science, 126(May), 29–36. 10.1016/j.rvsc.2019.08.021.

Goldschmidt, M. H., Peña, L., & Zappulli, V. (2017). Tumors of the Mammary Gland. In Meuten D.J. (Ed.), Tumors in Domestic Animals. (5th ed.), 723–765. John Wiley & Sons Inc.

Kim, J. H., Yu, C. H., Yhee, J. Y., Im, K. S., & Sur, J. H. (2010). Lymphocyte infiltration, expression of interleukin (IL) -1, IL-6 and expression of mutated breast cancer susceptibility gene-1 correlate with malignancy of canine mammary tumours. Journal of Comparative Pathology, 142(2–3), 177–186. 10.1016/j.jcpa.2009.10.023.

Kim, J. H., Chon, S. K., Im, K. S., Kim, N. H., & Sur, J. H. (2013). Correlation of tumor-infiltrating lymphocytes to histopathological features and molecular phenotypes in canine mammary carcinoma: A morphologic and immunohistochemical morphometric study. Canadian Journal of Veterinary Research, 77(2), 142–149.

Knief, J., Reddemann, K., Petrova, E., Herhahn, T., Wellner, U., & Thorns, C. (2016). High density of tumor-infiltrating b-lymphocytes and plasma cells signifies prolonged overall survival in adenocarcinoma of the esophagogastric junction. Anticancer Research, 36(10), 5339–5345. 10.21873/anticanres.11107.

Lopes-Neto, B. E., Caroline, S., Souza, B., Bouty, L. M., Jonas, G., Santos, L., & Oliveira, E. S. (2017). CD4+, CD8+, FoxP3+ and HSP60+ Expressions in Cellular Infiltrate of Canine Mammary Carcinoma in Mixed Tumor. Acta Scientiae Veterinariae, 55(85), 1–8. 10.22456/1679-9216.80758.

Macchetti, A. H., Marana, H. R. C., Silva, J. S., De Andrade, J. M., Ribeiro-Silva, A., & Bighetti, S. (2006). Tumor-infiltrating CD4+ T lymphocytes in early breast cancer reflect lymph node involvement. Clinics, 61(3), 203–208. 10.1590/S1807-59322006000300004.

Mahmoud, S. M. A., Lee, A. H. S., Paish, E. C., MacMillan, R. D., Ellis, I. O., & Green, A. R. (2012). The prognostic significance of B lymphocytes in invasive carcinoma of the breast. Breast Cancer Research and Treatment, 132(2), 545–553. 10.1007/s10549-011-1620-1.

O’Neill, K., Guth, A., Biller, B., Elmslie, R., & Dow, S. (2009). Changes in regulatory T cells in dogs with cancer and associations with tumor type. Journal of Veterinary Internal Medicine, 23(4), 875–881. 10.1111/j.1939-1676.2009.0333.x.

Pérez, J., Day, M. J., Martín, M. P., Gonzalez, S., & Mozos, E. (1999). Immunohistochemical study of the inflammatory infiltrate associated with feline cutaneous squamous cell carcinomas and precancerous lesions (actinic keratosis). Veterinary Immunology and Immunopathology, 1;69(1):33-46. 10.1016/s0165-2427(99)00032-x.

Salgado, R., Denkert, C., Demaria, S., Sirtaine, N., Klauschen, F., Pruneri, G., Wienert, S., Van den Eynden, G., Baehner, F. L., Penault-Llorca, F., Perez, E. A., Thompson, E. A., Symmans, W. F., Richardson, A. L., Brock, J., Criscitiello, C., Bailey, H., Ignatiadis, M., Floris, G., … Loi, S. (2015). The evaluation of tumor-infiltrating lymphocytes (TILS) in breast cancer: Recommendations by an International TILS Working Group 2014. Annals of Oncology, 26(2), 259–271. 10.1093/annonc/mdu450.

Seixas, F., Antunes, D., & Pires, M. A. (2018). Immunohistochemical Analysis of T Lymphocytes (CD3 +) in Feline Mammary Lesions. Journal of Comparative Pathology, 158, 126. 10.1016/j.jcpa.2017.10.096.

Seixas, F., Palmeira, C., Pires, M. A., Bento, M. J., & Lopes, C. (2011). Grade is an independent prognostic factor for feline mammary carcinomas: A clinicopathological and survival analysis. Veterinary Journal, 187(1), 65–71. 10.1016/j.tvjl.2009.10.030.

Shen, M., Wang, J., & Ren, X. (2018). New insights into tumor-infiltrating B lymphocytes in breast cancer: Clinical impacts and regulatory mechanisms. Frontiers in Immunology, 9, 1–8. 10.3389/fimmu.2018.00470.

Tashireva, L., Denisov, E., Savelieva, O., Zavyalova, M., Kaigorodova, E., Slonimskaya, E., & Perelmuter, V. (2015). A14: Heterogeneity in breast tumor microenvironment: A report from one case. European Journal of Cancer Supplements, 13(1), 61. 10.1016/j.ejcsup.2015.08.109.

Togni, M., Masuda, E. K., Kommers, G. D., Fighera, R. A., & Irigoyen, L. F. (2013). Estudo retrospectivo de 207 casos de tumores mamários em gatas. Pesquisa Veterinária Brasileira, 33(3), 353–358. 10.1590/S0100-736X2013000300013.

Viste, J. R., Myers, S. L., Singh, B., & Simko, E. (2002). Feline mammary adenocarcinoma: Tumor size as a prognostic indicator. Canadian Veterinary Journal, 43(1), 33–37. 10.1111/j.1751-0813.2002.tb11342.x.

Weijer, K., & Hart, A. A. M. (1983). Prognostic Factors in Feline Mammary Carcinoma. JNCI: Journal of the National Cancer Institute, 70(4). 10.1093/jnci/70.4.709.

Wouters, M. C. A., & Nelson, B. H. (2018). Prognostic significance of tumor-infiltrating B cells and plasma cells in human cancer. Clinical Cancer Research, 24(24), 6125–6135. 10.1158/1078-0432.CCR-18-1481.

Yuen, G. J., Demissie, E., & Pillai, S. (2016). B Lymphocytes and Cancer: A Love–Hate Relationship. Trends in Cancer, 2(12), 747–757. 10.1016/j.trecan.2016.10.010.

Zappulli, V., Rasotto, R., Caliari, D., Mainenti, M., Peña, L., Goldschmidt, M. H., & Kiupel, M. (2015). Prognostic Evaluation of Feline Mammary Carcinomas: A Review of the Literature. Veterinary Pathology, 52(1), 46–60. 10.1177/0300985814528221.

Published

27/03/2021

How to Cite

BERSELLI, M.; GUIM, T. N.; CASTRO, C. C. de; CORRÊA, L. G.; ROSSATO, A. D. P.; SILVA, L. M. C. da; GRECCO, F. B. .; BRUHN, F. R. P. .; FERNANDES, C. G. Infiltrating inflammatory cells: Profile and distribution in feline mammary carcinomas. Research, Society and Development, [S. l.], v. 10, n. 3, p. e57410313651, 2021. DOI: 10.33448/rsd-v10i3.13651. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/13651. Acesso em: 12 apr. 2021.

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Section

Agrarian and Biological Sciences