Infiltrating inflammatory cells: Profile and distribution in feline mammary carcinomas
DOI:
https://doi.org/10.33448/rsd-v10i3.13651Keywords:
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.
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.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Michele Berselli; Thomas Normanton Guim; Clarissa Caetano de Castro; Luísa Grecco Corrêa; Andressa Dutra Piovesan Rossato; Luísa Mariano Cerqueira da Silva; Fabiane Borelli Grecco; Fabio Raphael Pascoti Bruhn; Cristina Gevehr Fernandes
![Creative Commons License](http://i.creativecommons.org/l/by/4.0/88x31.png)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.