Table 1 - uploaded by Fernando Tecles
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Staging of canine mammary tumors (excluding inflammatory carcinoma) modified from the World Health Organization.* ,13,15
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Acute phase proteins (APPs) are proteins whose concentrations in serum change after any inflammatory stimulus or tissue damage. The aim of the current study was to evaluate 3 positive APPs (C-reactive protein, serum amyloid A, and haptoglobin) and 1 negative APP (albumin) in female dogs with mammary neoplasia. Acute phase proteins were studied in 7...
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Context 1
... Recorded data regarding tumor size, lymph node involvement, and metastasis were used to classify tumors according to the TNM system. Subsequent staging (stages I-V) of the neoplasms was based on the criteria in Table 1. Concurrent diseases, such as pyometra, mastitis, or other inflammatory diseases, were observed in 18 dogs that were grouped separately (concomitant disease group). ...
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Neoplasia mamária benigna diagnosticada por punção aspirativa por agulha fina em porquinho da Índia (Cavia porcellus)] ABSTRACT -Cytology is a well established research technique in human and veterinary medicine, but it is rarely used in small rodents. Spontaneous tumors are relatively uncommon in guinea pigs and those described in literature inclu...
Citations
... In addition to these specific markers, acute phase proteins have been intensively studied in women with breast cancer, especially their significance as prognostic indicators [13,14]. Some studies were conducted also in female dogs with mammary tumors, which were oriented to the analysis of main canine acute phase proteins (C-reactive protein, serum amyloid A, haptoglobin) and the magnitude of their increase [15,16]. However, it has not yet been studied whether mammary tumors may cause alterations in the serum protein electrophoretic pattern and distribution of protein fractions. ...
... Furthermore, the animals were brought to the hospital at a different stage of tumor formation, which may also explain the great variability among the measured values. In the study conducted by Tecles et al. [15], significantly higher concentrations of SAA were obtained only in those bitches with mammary tumors that had metastasis or the diameter of tumor was greater than 5 cm and had ulcerations. On the other hand, bitches with mammary tumors in the I-III stages of the disease presented only weak inflammatory response. ...
Alterations in the serum protein pattern may be associated with many diseases, including neoplastic processes. In veterinary medicine, these changes are poorly understood. Therefore, this study was aimed at the analysis of the distribution of blood serum protein fractions separated by agarose gel electrophoresis, and at the determination of the concentrations of main acute phase proteins in bitches with mammary gland neoplasia. The evaluation was conducted on twelve female dogs with palpable single or multiple nodules in the parenchyma of the mammary gland and on ten tumor-free clinically healthy bitches to compare the possible differences in the obtained results. Blood serum was used to perform agarose gel electrophoresis of the main blood serum protein fractions and to analyze the concentrations of total serum proteins and the following canine acute phase proteins: serum amyloid A, haptoglobin, C-reactive protein and α 1-acid glycoprotein. The concentrations of total serum proteins were slightly higher in bitches with mammary gland tumors. Serum protein electrophoresis showed lower mean concentrations of albumin and α 1-globulins in the affected dogs, while the concentrations of α 2-and β 1-globulins were significantly higher (P=0.0032 and P=0.0021, respectively) compared to dogs without mammary gland tumors. In the concentrations of acute phase proteins, significantly higher mean concentrations of C-reactive protein and haptoglobin were obtained in dogs with mammary tumors (P=0.0025 and P=0.0002, respectively). The values of α 1-acid glycoprotein did not vary markedly between the bitches with and without mammary tumors. Presented data suggest that neoplastic processes in the mammary gland may also alter the electrophoretic pattern of blood serum proteins and induce changes in the production of some inflammatory proteins.
... In this study, there were dogs with life-threatening diseases in group B such as acute pancreatitis, pyometra and malignant tumors with metastasis that might cause significant inflammation and death (10,(34)(35)(36)(37). In contrast, group A included dogs with diseases with localized lesions that do not cause severe inflammation, such as mitral valve insufficiency, mammary gland tumors (WHO stage I) and intervertebral disk protrusion; these characteristics are similar to data previously reported in veterinary studies (18,38,39). According to our results, PAB was a good marker to differentiate group B from group A, and a decreased PAB concentration was present in dogs suffering from inflammation and was inversely correlated with the severity of inflammation. ...
Introduction
Prealbumin (PAB) is a plasma protein synthesized in the hepatic parenchymal cells. PAB has a short half-life (~2 days), and its concentration is affected by changes in transcapillary escape. Measurement of PAB is widely used in hospitalized patients in human medicine due to its decreasing concentration in states of inflammation and malnutrition. However, only a few studies are available in dogs. The aim of this study is to determine whether the plasma PAB concentration decreases in dogs with inflammation and to evaluate the relationship between the plasma PAB concentration and inflammation-related parameters in dogs.
Methods
A total of 94 dogs were divided into healthy (n = 33) and diseased (n = 61) groups. These were further divided into group A (n = 24) and group B (n = 37) according to plasma C-reactive protein (CRP) levels. Group A included dogs with a plasma CRP < 10 mg/L, and group B consisted of dogs with a plasma CRP ≥ 10 mg/L. Patient signalment, history, physical examination findings, hematologic and biochemical parameters, various inflammatory markers, and plasma PAB levels were investigated and compared between groups.
Results
The plasma PAB concentration was found to be lower in group B than in the other groups (p < 0.001), but no statistical difference was found when comparing the control group and group A (p > 0.05). A plasma PAB < 6.3 mg/dL predicted an increased CRP level (10 mg/L or greater) with a sensitivity of 89.5% and a specificity of 86.5%. Receiver operating characteristic curve analysis revealed that the area under the curve for PAB was higher than that for the white blood cell count, neutrophil count, albumin level, lactate level, neutrophil-to-lymphocyte ratio, and neutrophil percentage-to-albumin ratio. In addition, the PAB concentration was significantly negatively correlated with the CRP concentration (r = −0.670, p < 0.001).
Conclusion
In conclusion, this is the first study to demonstrate the clinical usefulness of the plasma PAB concentration as an inflammatory marker in dogs. These findings suggest that measuring the plasma PAB concentration along with the CRP concentration may be more useful for evaluating inflammation than measuring CRP alone in canine patients.
... An increase in clinical blood parameters related to infammation may indicate the existence of cancer or tumors. Te concentration of the C-reactive protein (CRP), an acute phase protein, is rapidly rising in response to trauma [8], infammation [9][10][11], infection [12][13][14][15][16], and several malignancies [8,[17][18][19]. Te elevated CRP levels are the essential information for diagnosis and prognosis not only in human medicine [20][21][22] but also in veterinary clinical medicine [16,17,[23][24][25][26][27]. ...
... Te concentration of the C-reactive protein (CRP), an acute phase protein, is rapidly rising in response to trauma [8], infammation [9][10][11], infection [12][13][14][15][16], and several malignancies [8,[17][18][19]. Te elevated CRP levels are the essential information for diagnosis and prognosis not only in human medicine [20][21][22] but also in veterinary clinical medicine [16,17,[23][24][25][26][27]. A previous report identifed CRP and serum amyloid A (SAA) as diagnostic markers and prognostic indications after treatment of infammation for the bacterial pneumonia [15]. ...
... CRP, SAA, and haptoglobin were detected and a signifcant increase in the canine mammary cancer such as anaplastic carcinoma, complex adenocarcinoma, simple adenocarcinoma, and SCC with metastasis, which characterized in the clinical stage IV-V or by a mass diameter greater than 5 centimeters with ulceration and secondary infammation, was seen. Conversely, these dogs had the decreasing albumin concentration [17]. Moreover, canine mammary carcinoma showed a high concentration of CRP. ...
Canine oral cancers have a poor prognosis and are related to chronic inflammation. This may pose a risk of secondary bacterial infection. This study aimed to compare the bacteria isolated from oral swab samples, values of C-reactive proteins (CRPs), and clinical blood profiles of dogs with and without oral mass. A total of 36 dogs were divided in three groups: no oral mass (n = 21), oral mass (n = 8), and metastasis groups (n = 7). Significantly, both the clinical groups (the oral mass group and metastasis group) showed anemia, a decrease in the albumin-to-globulin ratio (AGR), and an increase in the neutrophil-to-lymphocyte ratio (NLR), globulin-to-albumin ratio (GAR), CRP, and CRP-to-albumin ratio (CAR) compared to the normal group. CAR showed an increasing trend in the oral mass and metastasis groups (10 times and 100 times, respectively) compared to the no oral mass group ( P < 0.001 ). Neisseria spp. (20.78%) was the main isolated bacteria in all groups. The main genera in the no oral mass group were Neisseria spp. (28.26%), Pasteurella spp. (19.57%), and Staphylococcus spp. (19.57%). Neisseria spp., Staphylococcus spp., Klebsiella spp., and Escherichia spp. were found equally (12.5%) in the oral mass group. Escherichia spp. (26.67%), Pseudomonas spp. (13.33%), and Staphylococcus spp. (13.33%) were the main genera in the metastasis group. Interestingly, Neisseria spp. decreased in the clinical groups (Fisher’s exact = 6.39, P = 0.048 ), and Escherichia spp. increased in the metastasis group (Fisher’s exact = 14.00, P = 0.002 ). The difference of oral bacteria in clinical dogs compared to healthy dogs may be related to microbiome alterations, and both the clinical groups showed the increment of inflammatory biomarkers. This suggested that further studies should be conducted on the correlation between the specific bacteria, CRP, blood clinical parameters, and type of canine oral mass.
... Regarding the CRP levels, female dogs which had larger nodules (Szczubiał et al., 2018), ulcerated skin (Planellas et al., 2009;Szczubiał et al., 2018), distant metastasis (Szczubiał et al., 2018), and high clinical stages (Tecles et al., 2009) exhibited higher concentrations of CRP. Campos et al. (2012) demonstrated a positive correlation only between LDH concentration and clinical staging. ...
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.
... Of these cases, hematopoietic tumors might provoke the greatest elevation. In addition, disseminated tumors tend to cause higher spikes of CRP than localized tumors, which may not raise CRP at all (e.g., leiomyosarcoma, mammary gland tumors) [9,94]. In dogs with multicentric lymphoma, low, physiological CRP level was shown to be related to obtaining remission [33]. ...
... It was hypothesized that unless there is a metastasis or the tumor is greater than 5 cm in diameter, the lesions might be too poor of a stimulus for APPs production. It is unknown why stage IV showed higher concentrations than V [94]. ...
Simple Summary: C-reactive protein is a major positive acute phase protein in dogs. It is commonly used as a marker of inflammation that, although nonspecific, is highly sensitive. The high clinical value lies in its rapid response and relatively short half-life time; these qualities make the C-reactive protein a good therapeutic guide; among others, it can be used to determine when an antimicrobial therapy could be ceased. Various tests are available on the market and the measurement is becoming a part of routine biochemistry blood panels in many countries. Although it is very useful, especially in conjunction with white blood cell count or other acute phase response proteins measurements, it does not allow a complete evaluation as a single parameter. Abstract: Acute phase response is a nonspecific reaction to disturbances in homeostasis during which the production of some Acute Phase Proteins (APPs) is stimulated; they are sensitive but nonspecific markers of systemic inflammatory processes. The major positive APP in dogs is the C-reactive protein (CRP). The dynamic of its concentration changes fast, rising and decreasing rapidly with the onset and removal of the inflammatory stimulus. It increases within the first 4-24 h after the stimulus and reaches up to a 50-100-fold increase of the baseline level. It has been documented that this APP's concentration is elevated during several diseases, such as pyometra, panniculitis, acute pancreatitis, polyarthritis, sepsis, immune-mediated hemolytic anemia, and neoplasia in dogs. In clinical practice, canine CRP is mostly measured to detect and monitor systemic inflamma-tory activity and the efficacy of treatments, because it is a more sensitive marker than shifts in leu-kocyte counts. Blood serum CRP concentration is becoming a part of routine biochemistry panels in many countries. In this article, changes in CRP concentration and its clinical application in healthy and diseased dogs are discussed.
... SAA fluctuation has also been tested in mammary gland tumors that represent up to 52% of neoplasm in female dogs, they and are diagnosed as malignant in up to 50% of cases [46]. In their work, Tecles et al. [24] found that, in female dogs with mammary gland tumors, APP secretion is dependent upon factors such as the presence of metastasis, the large size of the primary mass, ulceration, or the secondary inflammation of the neoplasm. The preliminary results obtained by Tecles et al. deserves to be further explored to better ascertain a possible application of APPs in the monitoring of therapy and long-term prognosis of mammary tumors in female dogs. ...
The investigation of acute phase proteins in veterinary medicine has opened the doors towards the identification and use of new markers for a timely assessment of health status in both companion and food-producing animals. The aim of this paper is to review the literature available on the use of serum amyloid A (SAA), an acute phase protein, for the diagnosis and monitoring of reproductive disorders in animals. This review critically appraises the usefulness of such marker in clinical practice and summarizes the current state of knowledge. Recent advances in the diagnosis and monitoring of reproductive diseases are presented, highlighting where SAA evaluation may enhance early diagnostic tools for dogs, cats, cattle, and equines.
... The complex relationship recently described between mammary tumor, inflammation, and alterations in cellular metabolism have highlighted the rationale for combined assessment of cancer antigen 15-3 (CA 15-3), C-reactive protein (CRP), and lactate dehydrogenase (LDH) (Hanahan & Weinberg, 2011). In CMTs, CA 15-3 (Campos et al., 2012;Campos et al., 2015;Manuali et al., 2012;Valencakova-Agyagosova et al., 2014), CRP (Planellas et al., 2009;Tecles et al., 2009;Szczubiał et al., 2018), and LDH (Campos et al., 2012) have been suggested as good biomarkers. ...
... Although elevated CRP and LDH are not the biomarkers of cancer, they may serve as the cofactors that increase the diagnostic accuracy to detect CMT. Female dogs that exhibited larger nodules (Szczubiał et al., 2018), ulcerated skin (Planellas et al., 2009;Szczubiał et al., 2018), distant metastasis (Szczubiał et al., 2018), and high clinical stages (Tecles et al., 2009) exhibited higher concentrations of CRP. Campos et al. (2012) demonstrated a positive correlation between LDH concentration and clinical staging. ...
Inflammatory mammary carcinoma (IMC) is characterized by the presence of any subtype of aggressive carcinoma in association with an intense inflammatory reaction, in addition to the presence of tumor emboli. Considering IMC as a type of cancer with chronic inflammation, the complex relationship between inflammation, and alterations in cellular metabolism have highlighted the rationale assessment of cancer antigen 15-3 (CA 15-3), c-reactive protein (CRP), and lactate dehydrogenase (LDH). The present report had the objective to describe a rare case of adenosquamous carcinoma in mammary gland of a 10-year-old bitch, 7 kg, sexually intact, mixed-breed and how CA 15-3, CRP and LHD helped to determinate the clinical presentation of inflammatory carcinoma and the prognosis. Complete clinical staging, cell blood count and renal, and hepatic biochemistry was performed and did not reveal any significant abnormalities. CA 15-3 (9.46 IU/mL), CRP (5.3 mg/L), and LDH (287 U/L) were all above the references values reported by the literature. Although adenosquamous carcinoma of the mammary gland with inflammatory presentation in dogs is rare, the association of serum biomarkers could improve the patient's prognosis evaluation.
... For example, it is known that albumin, which accounts for 35% to 50% of STP, is a negative acute-phase protein that can decrease in response to inflammation of any cause, including cancer. 37 It has been shown that dogs with mammary tumors and clinically detectable metastases have significantly decreased serum albumin concentrations, compared with dogs that have mammary tumors without metastases, 38 and that several positive acute-phase proteins (produced in response to inflammation) are known to be variably increased in the serum of dogs with mammary carcinoma and other cancers. 39 A possible relationship between splenic hemangiosarcoma and the presence of abnormal circulating RBCs, including acanthocytes, schistocytes, and nRBCs, has long been recognized. ...
Objective:
To develop a multivariable model and online decision-support calculator to aid in preoperative discrimination of benign from malignant splenic masses in dogs.
Animals:
522 dogs that underwent splenectomy because of splenic masses.
Procedures:
A multivariable model was developed with preoperative clinical data obtained retrospectively from the records of 422 dogs that underwent splenectomy. Inclusion criteria were the availability of complete abdominal ultrasonographic examination images and splenic histologic slides or histology reports for review. Variables considered potentially predictive of splenic malignancy were analyzed. A receiver operating characteristic curve was created for the final multivariable model, and area under the curve was calculated. The model was externally validated with data from 100 dogs that underwent splenectomy subsequent to model development and was used to create an online calculator to estimate probability of splenic malignancy in individual dogs.
Results:
The final multivariable model contained 8 clinical variables used to estimate splenic malignancy probability: serum total protein concentration, presence (vs absence) of ≥ 2 nRBCs/100 WBCs, ultrasonographically assessed splenic mass diameter, number of liver nodules (0, 1, or ≥ 2), presence (vs absence) of multiple splenic masses or nodules, moderate to marked splenic mass inhomogeneity, moderate to marked abdominal effusion, and mesenteric, omental, or peritoneal nodules. Areas under the receiver operating characteristic curves for the development and validation populations were 0.80 and 0.78, respectively.
Conclusions and clinical relevance:
The online calculator (T-STAT.net or T-STAT.org) developed in this study can be used as an aid to estimate the probability of malignancy in dogs with splenic masses and has potential to facilitate owners' decisions regarding splenectomy.
... In human and animal patients with neoplasia and in absence of an additional disease, major inflammatory reactions are also a characteristic of malignant tumors (e.g. mammary carcinomas, lymphatic neoplasms) [10,34]. This is in accordance with our study, where CRP values > 100 mg/l were only found in association with malignant and not benign neoplasia. ...
... This is in accordance with our study, where CRP values > 100 mg/l were only found in association with malignant and not benign neoplasia. Benign neoplasia is seldom described to cause major inflammatory reactions [9] and might be associated with ulceration in these cases [10,34]. In human medicine, a proportion of about 25-40% of patients with malignant cancer has associated infectious or noninfectious mild to severe inflammation, which may be accompanied by a systemic acute phase reaction [35][36][37]. ...
... In human medicine, a proportion of about 25-40% of patients with malignant cancer has associated infectious or noninfectious mild to severe inflammation, which may be accompanied by a systemic acute phase reaction [35][36][37]. A similar explanation might be true for canine patients in general [34] and for the marked acute phase reaction seen in cancer patients in our study. Nevertheless, diagnostics concerning a possible secondary bacterial infection are indicated in patients with tumor and high CRP values [8,20]. ...
Background:
In human medicine, extremely high CRP (C-reactive protein) concentrations > 100 mg/l are indicators of bacterial infection and the need of antibiotic treatment. Similar decision limits for septic pneumonia are recommended for dogs but have not yet been evaluated for other organ systems. The aim of the retrospective study was to investigate the prevalence and evaluate dogs with CRP concentrations > 100 mg/l regarding the underlying etiology, the affected organ system and the prognostic significance.
Results:
Prevalence of CRP > 100 mg/l was investigated in dogs presented between 2014 and 2015 and was 12%. For evaluation of etiology and organ systems, dogs with CRP > 100 mg/l presented between 2014 and 2016 were enrolled. Dogs were classified into 4 main disease categories, i.e. inflammatory, neoplastic, tissue damage or "diverse". Diseases were assigned to the affected organ system. If an organ classification was not possible, dogs were classified as "multiple". 147 dogs with CRP 101-368 mg/l were included and classified into disease categories: 86/147 (59%) with inflammatory etiology (among these, 23/86 non-infectious, 44/86 infectious (33/44 bacterial), 19/86 inflammation non-classifiable), 31/147 (21%) tissue damage, 17/147 (12%) neoplastic (all malignant) and 13/147 (9%) diverse diseases. The affected organ systems included 57/147 (39%) multiple, 30/147 (20%) trauma, 21/147 (14%) gastrointestinal tract, 10/147 (7%) musculoskeletal system, 8/147 (5%) respiratory tract, 7/147 (5%) urinary/reproductive tract, 6/147 (4%) skin/subcutis/ear, 6/147 (4%) central/peripheral nervous system and 2/147 (1%) heart. The disease group (p = 0.081) or organ system (p = 0.17) did not have an impact on CRP. Based on CRP, a detection of bacterial infection was not possible. The prognostic significance was investigated by determining the 3-months survival and hospitalization rate in a subgroup with known outcome. The 3-months survival rate was 46/73 (63%) while the majority 66/73 (90%) of patients was hospitalized.
Conclusions:
CRP concentrations > 100 mg/l are occasionally seen in a clinic population. They indicate a severe systemic disease of various etiologies with guarded prognosis. Extremely high CRP concentrations do not allow a conclusion of the underlying etiology or an identification of bacterial inflammation.
... While haptoglobin is considered a moderate APP in dogs that increases by approximately 2-to 5-fold, albumin is a negative APP that decreases during inflammation [40]. In agreement with our results, increases in serum haptoglobin concentrations were observed in dogs with mammary tumors when compared to healthy controls [41,42], as well as in dogs with hemolymphatic, mesenchymal, and epithelial tumors [40,43,44]. The downregulation of albumin in serum in CMT bitches was further verified previously by a commercially available kit using an automated analyser, showing a decrease in albumin in dogs with CMT in comparison to controls. ...
The aim of this study was to evaluate changes in serum and saliva proteomes in canine mammary tumors (CMT) using a high-throughput quantitative proteomic analysis in order to potentially discover possible biomarkers of this disease. Proteomes of paired serum and saliva samples from healthy controls (HC group, n = 5) and bitches with CMT (CMT group, n = 5) were analysed using a Tandem Mass Tags-based approach. Twenty-five dogs were used to validate serum albumin as a candidate biomarker in an independent sample set. The proteomic analysis quantified 379 and 730 proteins in serum and saliva, respectively. Of those, 35 proteins in serum and 49 in saliva were differentially represented. The verification of albumin in serum was in concordance with the proteomic data, showing lower levels in CMT when compared to the HC group. Some of the modulated proteins found in the present study such as haptoglobin or S100A4 have been related to CMT or human breast cancer previously, while others such as kallikrein-1 and immunoglobulin gamma-heavy chains A and D are described here for the first time. Our results indicate that saliva and serum proteomes can reflect physiopathological changes that occur in CMT in dogs and can be a potential source of biomarkers of the disease.
