Animal Reproduction (AR)
Animal Reproduction (AR)

CA 15-3, CRP, and LDH correlates with prognostic parameters in canine mammary neoplasms

Breno Queiroz Pinheiro; Francisco Felipe de Magalhães; Francisco Wesley da Silva Alves; Isaac Neto Goes Silva; Augusto Manuel Rodrigues Faustino; Lúcia Daniel Machado da Silva

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The identification of putative prognostic factors in canine mammary neoplasms (CMNs) has been focused on tissue-specific biomarkers, but the serum biomarkers, including cancer antigen 15-3 (CA 15-3), c-reactive protein (CRP), and lactate dehydrogenase (LDH) have been demonstrated to display clinical application in cases of CMNs. The aim of the study was to evaluate the levels of these serum biomarkers and their association with well-established prognostic factors in CMNs. Samples from 15 female canines with CMNs and 15 clinically healthy ones were collected. The results were evaluated using the Tukey’s, Pearson, or Spearman tests. The cut-off point, sensitivity, specificity, and area under curve (AUC) were evaluated using the receiver operating characteristic (ROC) curve analysis in a logistic regression model (P<0.05). The levels of CA 15-3, CRP and LDH were significantly higher in the serum of female dogs with CMNs compared to the healthy ones. Moreover, these factors were positively correlated with ulceration, tumor size, histopathological grade, metastatic lymph node, and clinical staging. Female dogs with CMNs were found to exhibit highest serum levels of CA 15-3, CRP, and LDH. Therefore, they can be applied to improve the efficacy of the diagnosis and prognostic evaluation in casas of CMNs.


cancer, dog, mammary gland, serum biomarker


Allin KH, Nordestgaard BG. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci. 2011;48(4):155-70. PMid:22035340.

Araújo MR, Campos LC, Damasceno KA, Gamba CO, Ferreira E, Cassali GD. 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. 2016;106:121-30. PMid:27234549.

Baba OK, Sood NK, Gupta K. Clinical evaluation of glycoproteins and inflammatory cytokines in the serum of dogs affected with canine mammary cancer. Proc Natl Acad Sci, India, Sect B Biol Sci. 2019;89(4):1465-9.

Campos LC, Lavalle GE, Estrela-Lima A, Melgaço de Faria JC, Guimarães JE, Dutra ÁP, Ferreira E, Sousa LP, Rabelo ÉM, Vieira da Costa AF, Cassali GD. CA15.3, CEA and LDH in dogs with malignant mammary tumors. J Vet Intern Med. 2012;26(6):1383-8. PMid:23113715.

Campos LC, Silva JO, Santos FS, Araújo MR, Lavalle GE, Ferreira E, Cassali GD. Prognostic significance of tissue and serum HER2 and MUC1 in canine mammary cancer. J Vet Diagn Invest. 2015;27(4):531-5. PMid:26179096.

Carney PC, Ruaux CG, Suchodolski JS, Steiner JM. Biological variability of C-reactive protein and specific canine pancreatic lipase immunoreactivity in apparently healthy dogs. J Vet Intern Med. 2011;25(4):825-30. PMid:21564294.

Cassali GD, Jark PC, Gamba C, Damasceno KA, Estrela-Lima A, Nardi AB, et al. Consensus regarding the diagnosis, prognosis and treatment of canine and feline mammary tumors-2019. Braz J Vet Pathol. 2020;13(3):555-74.

Darlix A, Lamy PJ, Lopez-Crapez E, Braccini AL, Firmin N, Romieu G, Thezenas S, Jacot W. Serum HER2 extra-cellular domain, S100ß and CA 15-3 levels are independent prognostic factors in metastatic breast cancer patients. BMC Cancer. 2016;16(1):428. PMid:27387327.

David JM, Hamilton DH, Palena C. MUC1 upregulation promotes immune resistance in tumor cells undergoing brachyury-mediated epithelial- mesenchymal transition. OncoImmunology. 2016;5(4):e1117738. PMid:27141403.

Di Gioia D, Blankenburg I, Nagel D, Heinemann V, Stieber P. Tumor markers in the early detection of tumor recurrence in breast cancer patients: CA 125, CYFRA 21-1, HER2 shed antigen, LDH and CRP in combination with CEA and CA 15-3. Clin Chim Acta. 2016;461:1-7. PMid:27451906.

Elston CW, Ellis IO. Assessment of histological grade Systemic pathology: the breast. 3rd ed. London: Churchill Livingstone; 1998.

Ferreira E, Bertagnolli AC, Cavalcanti MF, Schmitt FC, Cassali GD. The relationship between tumour size and expression of prognostic markers in benign and malignant canine mammary tumours. Vet Comp Oncol. 2009;7(4):230-5. PMid:19891693.

Han Y, Mao F, Wu Y, Fu X, Zhang W, Zhu X, Zhou S, Zhang W, Sun Q, Zhao Y. Prognostic role of C-reactive protein in breast cancer: a systematic review and meta-analysis. Int J Biol Markers. 2011;26(4):209-15. PMid:22139643.

Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4(1):45-60. PMid:14681689.

Huang X, Li X, Xie X, Ye F, Chen B, Song C, Tang H, Xie X. High expressions of LDHA and AMPK as prognostic biomarkers for breast cancer. Breast. 2016;30:39-46. PMid:27598996.

Kabel AM. Tumor markers of breast cancer: new prospectives. J Onc Sci. 2017;3(1):5-11.

Kaneko JJ, Harvey JW, Bruss ML. Clinical biochemistry of domestic animals. 6th ed. San Diego: Academic Press; 2008.

Kaszak I, Ruszczak A, Kanafa S, Kacprzak K, Król M, Jurka P. Current biomarkers of canine mammary tumors. Acta Vet Scand. 2018;60(1):66. PMid:30373614.

Kjelgaard-Hansen M, Jensen AL, Kristensen AT. Evaluation of a commercially available human C-reactive protein (CRP) turbidometric immunoassay for determination of canine serum CRP concentration. Vet Clin Pathol. 2003;32(2):81-7. PMid:12833223.

Koukourakis MI, Kontomanolis E, Giatromanolaki A, Sivridis E, Liberis V. Serum and tissue LDH levels in patients with breast/gynaecological cancer and benign diseases. Gynecol Obstet Invest. 2009;67(3):162-8. PMid:19088479.

Manuali E, De Giuseppe A, Feliziani F, Forti K, Casciari C, Marchesi MC, Pacifico E, Pawłowski KM, Majchrzak K, Król M. CA 15-3 cell lines and tissue expression in canine mammary cancer and the correlation between sérum levels and tumour histological grade. BMC Vet Res. 2012;8(1):86. PMid:22726603.

Marchesi MC, Manuali E, Pacifico E, Ferri C, Romagnoli M, Mangili V, Fruganti G. Cancer antigen 15/3: possible diagnostic use in veterinary clinical oncology. Preliminary study. Vet Res Commun. 2010;34(S1, Suppl 1):S103-6. PMid:20432064.

Marconato L, Crispino G, Finotello R, Mazzotti S, Salerni F, Zini E. Serum lactate dehydrogenase activity in canine malignancies. Vet Comp Oncol. 2009;7(4):236-43. PMid:19891694.

Marconato L, Crispino G, Finotello R, Mazzotti S, Zini E. Evaluation of lactate dehydrogenase activity to predict recurrence of lymphoma in dogs. Vet Rec. 2010;166(22):695.

Naik A, Decock J. Lactate metabolism and immune modulation in breast cancer: a focused review on triple negative breast tumors. Front Oncol. 2020;10:598626. PMid:33324565.

Nunes FC, Campos CB, Teixeira SV, Bertagnolli AC, Lavalle GE, Cassali GD. Epidemiological, clinical and pathological evaluation of overall survival in canines with mammary neoplasms. Arq Bras Med Vet Zootec. 2018a;70(6):1714-22.

Nunes FC, Damasceno KA, Campos CB, Bertagnolli AC, Lavalle GE, Cassali GD. Mixed tumors of the canine mammary glands: evaluation of prognostic factors, treatment, and overall survival. Vet Anim Sci. 2018b;7:100039. PMid:32734062.

Planellas M, Bassols A, Siracusa C, Saco Y, Giménez M, Pato R, Pastor J. Evaluation of serum haptoglobin and C-reactive protein in dogs with mammary tumors. Vet Clin Pathol. 2009;38(3):348-52. PMid:19392756.

Roberto GB, Ziliotto L, Seki MC. Avaliação comparativa de dosagem do marcador tumoral CA 15-3 em cadelas hígidas ou com neoplasia mamária. Pesq Vet Bras. 2018;38(9):1800-7.

Ryu MO, Kim BG, Choi US, Baek KH, Song YK, Li Q, Seo KW, Ryeom S, Youn HY, Bhang DH. Extracellular cyclic adenosine monophosphate-dependent protein kinase A autoantibody and C-reactive protein as serum biomarkers for diagnosis of cancer in dogs. Vet Comp Oncol. 2019;17(1):99-106. PMid:30411459.

Selting KA, Ringold R, Husbands B, Pithua PO. Thymidine kinase type 1 and C-reactive protein concentrations in dogs with spontaneously occurring cancer. J Vet Intern Med. 2016;30(4):1159-66. PMid:27214230.

Shao Y, Sun X, He Y, Liu C, Liu H. Elevated levels of serum tumor markers CEA and CA15-3 are prognostic parameters for different molecular subtypes of breast cancer. PLoS One. 2015;10(7):e0133830. PMid:26207909.

Shimura T, Shibata M, Gonda K, Murakami Y, Noda M, Tachibana K, Abe N, Ohtake T. Prognostic impact of interleukin-6 and c-reactive protein onpatients with breast cancer. Oncol Lett. 2019;17(6):5139-46. PMid:31186728.

Sorenmo KU, Worley DR, Zappulli V. Tumors of the Mammary Gland. In: Vail DM, Thamm DH, Liptak JM, editors. Small animal clincal oncology. 6th ed. St. Louis: Elsevier; 2020.

Szczubiał M, Dabrowski R, Łopuszyński W, Bochniarz M, Krawczyk M. Changes in serum neopterin and C-reactive protein concentrations in female dogs with mammary gland tumours. Pol J Vet Sci. 2018;21(4):691-6. PMid:30605283.

Tecles F, Caldín M, Zanella A, Membiela F, Tvarijonaviciute A, Subiela SM, Cerón JJ. Serum acute phase protein concentrations in female dogs with mammary tumors. J Vet Diagn Invest. 2009;21(2):214-9. PMid:19286500.

Valencakova-Agyagosova A, Frischova Z, Sevcikova Z, Hajurka J, Lepej J, Szakallova I, Kredatusova G, Nagy V, Ledecky V. Determination of carcinoembryonic antigen and cancer antigen (CA 15-3) in bitches with tumours on mammary gland: preliminary report. Vet Comp Oncol. 2014;12(3):205-14. PMid:22947252.

Yamagami T, Kobayashi T, Takahashi K, Sugiyama M. Prognosis for canine malignant mammary tumours based on TNM and histologic classification. J Vet Med Sci. 1996;58(11):1079-83. PMid:8959655.

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