scholarly journals Paraneoplastic Hypercalcemia Secondary to Canine Mammary Tumors

2018 ◽  
Vol 44 (1) ◽  
pp. 7
Author(s):  
Talita Mariana Morata Raposo-Ferreira ◽  
Giovanna Rossi Varallo ◽  
Sabryna Gouveia Calazans ◽  
Paulo Cesar Jark ◽  
Rosana Da Cruz Lino Salvador ◽  
...  
Keyword(s):  
Serum Calcium ◽  
Tumor Resection ◽  
Clinical Signs ◽  
Tumor Grade ◽  
Mammary Tumors ◽  
Clinical Staging ◽  
Clinical Test ◽  
Mammary Carcinomas ◽  
Canine Mammary Tumors ◽  
Paraneoplastic Hypercalcemia

Background: Paraneoplastic syndromes are complexes symptom that occur at a distinct site from the primary tumor or its metastasis by the production of hormone by the tissue in which the tumor appears. Paraneoplastic hypercalcemia is associated with an abnormal elevation of serum calcium levels and the mainly tumor related to this syndrome in canine is lymphoma, anal sac apocrine gland adenocarcinoma and multiple myeloma. In mammary tumors, the most frequent tumor that affect female dogs, this syndrome was also observed. The aims of this study were to evaluate serum calcium levels in female dogs with malignant mammary tumors and correlate calcium levels with clinicopathological parameters.Materials, Methods & Results: It was evaluated fifty-one female dogs with mammary carcinomas (simple carcinomas and carcinoma in mixed tumors) for serum calcium levels using colorimetric test. Clinical-histopathological data as spray status, pseudopregnancy, tumor size, ulceration, clinical staging, histopathological type and tumor grade were also evaluated in association with serum calcium levels. All dogs were treated with unilateral mastectomy. It was observed that 18 animals (35%) had calcium serum levels increased (>11.5 mg/dL) and 56% (10/18 cases) of these animals had serum calcium levels higher than 12 mg/dL. All dogs with hypercalcemia were asymptomatic, including two female dogs that presented the highest levels (13.43 mg/dL and 14.28 mg/dL). Hypercalcemia of malignancy was related to mammary carcinomas after the exclusion of other causes of hypercalcemia through laboratory tests (complete blood count and serum biochemistry) and abdominal ultrasound. No correlation was verified between the corrected serum calcium values with clinical and histopathological parameters evaluated.Discussion: In this study, it was observed a high incidence of paraneoplastic hypercalcemia associated with canine mammary tumors (35%). In humans, this syndrome is related in up to 10% of all patients with advanced cancer and with worse prognosis. The most frequent clinical signs of hypercalcemia are nonspecific and can be confused with other diseases, such as polyuria, polydipsia, anorexia, constipation, lethargy and weakness. The treatment of this syndrome is based on tumor resection and when necessary other treatments can be performed with fluid containing 0.9% sodium chloride, furosemide, prednisolone and calcitonin. Patients with asymptomatic or mildly symptomatic hypercalcemia (calcium levels <12 mg/ dL) do not require immediate treatment. Clinical signs occur more frequently with serum calcium levels higher than 15 mg/dL. Calcium levels higher than 18 mg/dL are considered a medical emergency and the clinical signs observed are trigger seizures, cardiac arrhythmia, acute renal failure and death. Most animals of this study presented mild hypercalcemia, that could justify the absence of clinical signs related to this syndrome, and the treatment for this syndrome was the tumor removal. The high serum calcium levels did not show correlation with more aggressive tumors and poorer prognosis, conditions evaluated by histological type, tumor grade and clinical stage. The evaluation of serum calcium levels is an important clinical test to be done in female dogs with mammary tumors, besides to be an affordable and technically simple test. The clinical signs related to this syndrome are nonspecific and may be confused with other diseases commonly observed in older dogs. The data suggest that there are no correlation between serum calcium levels with aggressiveness of canine mammary tumors and with other clinical features.

Involvement of Nestin in the Progression of Canine Mammary Carcinoma

2021 ◽  
pp. 030098582110186
Author(s):  
Hisashi Yoshimura ◽  
Maiko Moriya ◽  
Ayaka Yoshida ◽  
Masami Yamamoto ◽  
Yukino Machida ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mammary Carcinoma ◽  
Mammary Tumors ◽  
Carcinoma Cells ◽  
Nestin Expression ◽  
Mammary Carcinomas ◽  
Canine Mammary Carcinoma ◽  
Canine Mammary Tumors ◽  
Mammary Carcinoma Cells ◽  
Luminal Epithelial Cells

Nestin, a class VI intermediate filament protein, is known to be expressed in various types of human neoplasms, including breast cancer, and is associated with their progression. However, its expression and role in canine mammary tumors remain unknown. We analyzed nestin expression in canine mammary tumors using in situ hybridization and immunohistochemistry. We also investigated its role in a canine mammary carcinoma cell line using RNA interference. Nestin expression was not observed in luminal epithelial cells of any of the 62 cases of benign mammary lesions examined, although myoepithelial cells showed its expression in most cases. In 16/50 (32%) primary mammary carcinomas and 6/15 (40%) metastases of mammary carcinomas, cytoplasmic nestin expression was detected in luminal epithelial cells. In luminal cells of primary mammary carcinomas, its expression was positively related to several pathological parameters that indicate high-grade malignancy, including histological grading ( P < .01), vascular/lymphatic invasion ( P < .01), Ki-67 index ( P < .01), and metastasis ( P < .05). Immunohistochemistry revealed that nestin expression was related to vimentin expression in mammary carcinomas ( P < .01). This relationship was confirmed using reverse transcription-quantitative polymerase chain reaction using 9 cell lines derived from canine mammary carcinoma ( P < .01). Finally, nestin knockdown in canine mammary carcinoma cells using small interfering RNA inhibited cell proliferation and migration based on WST-8, Boyden chamber, and cell-tracking assays. These findings suggest that nestin may at least partially mediate these behaviors of canine mammary carcinoma cells.

scholarly journals CD44 and CD24 Expression and Prognostic Significance in Canine Mammary Tumors

2018 ◽  
Vol 56 (3) ◽  
pp. 377-388 ◽  
Author(s):  
Bernadette Rogez ◽  
Quentin Pascal ◽  
Audrey Bobillier ◽  
François Machuron ◽  
Chann Lagadec ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Significance ◽  
Mammary Tumors ◽  
Clinicopathological Parameters ◽  
Tumor Type ◽  
High Grade ◽  
Mammary Carcinomas ◽  
Canine Mammary Tumors ◽  
Valuable Marker ◽  
High Level

CD44+/CD24– phenotype has been used to identify human and canine mammary cancer stem-like cells. In canine mammary tumors, CD44+/CD24– phenotype has been associated with high grade and lymph node infiltration. However, several studies have reported opposing results regarding the clinical significance of phenotypic groups formed by the combination of CD44 and CD24 in both human and canine mammary tumors. So far, no study has investigated the correlation between these phenotypes and survival in dogs. The aim of this study was to investigate the expression and distribution of CD44 and CD24 in canine mammary carcinomas and to correlate them with histological diagnosis and survival in a well-characterized cohort. Immunohistochemistry was performed in 96 mammary carcinomas with antibodies against CD44 and CD24. Expression of CD44+ and CD44+/CD24– phenotype was detected in 75 of 96 (78%) and 63 of 96 (65.6%) carcinomas, respectively. Their expression was associated with tumor type, occurring more often in tubular complex carcinomas than in solid carcinomas. CD44+/CD24– phenotype was associated with a better overall survival ( P = .001). CD24+ expression was detected in 52 of 96 tumors (54%) and CD44–/CD24+ phenotype in 39 of 96 tumors (40.6%). Both were associated with poor clinicopathological parameters (high grade, and emboli). No correlation with overall survival was observed. CD44+/CD24– expression was associated with a better prognosis and occurred at high frequency and high level, indicating that this phenotype is not suitable to detect cancer stem cells in canine mammary carcinomas. Although further studies are needed, our results suggest that CD24 may constitute a valuable marker of poor prognosis for canine mammary carcinomas.

scholarly journals A Statistical Analysis of Risk Factors and Biological Behavior in Canine Mammary Tumors: A Multicenter Study

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1687
Author(s):  
Giovanni P. Burrai ◽  
Andrea Gabrieli ◽  
Valentina Moccia ◽  
Valentina Zappulli ◽  
Ilaria Porcellato ◽  
...  
Keyword(s):  
Machine Learning ◽  
Risk Factors ◽  
Statistical Analysis ◽  
Multicenter Study ◽  
Malignant Tumors ◽  
Mammary Tumors ◽  
Supervised Machine Learning ◽  
Biological Behavior ◽  
Clinical Staging ◽  
Canine Mammary Tumors

Canine mammary tumors (CMTs) represent a serious issue in worldwide veterinary practice and several risk factors are variably implicated in the biology of CMTs. The present study examines the relationship between risk factors and histological diagnosis of a large CMT dataset from three academic institutions by classical statistical analysis and supervised machine learning methods. Epidemiological, clinical, and histopathological data of 1866 CMTs were included. Dogs with malignant tumors were significantly older than dogs with benign tumors (9.6 versus 8.7 years, p < 0.001). Malignant tumors were significantly larger than benign counterparts (2.69 versus 1.7 cm, p < 0.001). Interestingly, 18% of malignant tumors were smaller than 1 cm in diameter, providing compelling evidence that the size of the tumor should be reconsidered during the assessment of the TNM-WHO clinical staging. The application of the logistic regression and the machine learning model identified the age and the tumor’s size as the best predictors with an overall diagnostic accuracy of 0.63, suggesting that these risk factors are sufficient but not exhaustive indicators of the malignancy of CMTs. This multicenter study increases the general knowledge of the main epidemiologica-clinical risk factors involved in the onset of CMTs and paves the way for further investigations of these factors in association with CMTs and in the application of machine learning technology.

scholarly journals Amyloid in Canine Mammary Tumors

1985 ◽  
Vol 22 (4) ◽  
pp. 347-354 ◽  
Author(s):  
J. H. Vos ◽  
E. Gruys
Keyword(s):  
Epithelial Cells ◽  
Mammary Tumors ◽  
Histochemical Staining ◽  
Amyloid Deposition ◽  
Corpora Amylacea ◽  
Mammary Carcinomas ◽  
Canine Mammary Tumors ◽  
Stromal Tissue ◽  
Staining Methods ◽  
Neoplastic Epithelial Cells

In canine mammary carcinomas, amyloid was present as amyloid-containing corpora amylacea and as local deposits between neoplastic epithelial cells or in stromal tissue. Histochemical staining methods revealed that this amyloid was not of the AA-type amyloid and contained tryptophan. The possible pathogenesis of this amyloid deposition is discussed.

scholarly journals SAT-LB23 Paraneoplastic Hypercalcemia in a PTH Producing Adrenocortical Carcinoma - a Rare and Deadly Condition

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sven Gruber ◽  
Cong Tang ◽  
Mesut Berber ◽  
Stefan Fischli ◽  
David Penton-Ribas ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Adrenocortical Carcinoma ◽  
Tumor Resection ◽  
Steroid Synthesis ◽  
Endocrine Differentiation ◽  
Parathyroid Hormone Related Protein ◽  
Severe Hypercalcemia ◽  
H295r Cells ◽  
Paraneoplastic Hypercalcemia

Abstract Background: Hypercalcemia is a commonly encountered paraneoplastic manifestation of certain cancers with or without endocrine differentiation. However, the association between adrenocortical carcinoma (ACC) with paraneoplastic hypercalcemia is very rare, and therefore little is known about the cause and its relevance in the disease. Clinical Case: A 40-year-old woman presented in the hospital with a 5-month history of progressive flank pain with unintentional weight loss of 6 kg. MRI revealed a mass of 9x8.1x4.8 cm of the right adrenal gland with inhomogeneous contrast enhancement. Biochemical investigations provided evidence of endogenous hypercortisolism (24-hour urinary cortisol excretion [490 µg, n&lt;236 µg/l], 1mg dexamethasone suppression test [199 nmol/l, n&lt;50 nmol/l], ACTH [28 ng/l, n&lt;61 ng/l]) although the patient did not show any specific clinical sign of overt hypercortisolism. In addition, laboratory testing revealed an exceptionally high plasma level of calcium [max 3.67 mmol/l (albumin-corrected)] and low phosphate [min 0.26 mmol/l] in the setting of low PTH [6.4 ng/l, n&gt;15 ng/l] and PTHrP levels [&lt;0.50 pmol/l]. However, subsequent dilution unmasked a highly elevated PTH concentration of 2171.5 ng/l with persistent low PTHrP levels, indicating false low values due to a hook effect in the initial measurement. Levels of 1,25-dihydroxy vitamin D and 25-hydroxy vitamin D were in the normal range. A PET-CT provided no indications of metabolically active (osseous) metastases. After correction of the serum calcium towards tolerable values, the tumor was removed by open en bloc adrenalectomy. Histologic evaluation confirmed an ACC (TNM pT4 pN1 (2/3), L1, V1, high grade) despite missing immunohistochemically expression of classical adrenal markers (diagnosis of exclusion). Supplemental quantitative RT-PCR studies support the diagnosis of ACC by detecting significant SF-1 and CYP11B2 expression in the tumor cells. Further analyses provided evidence that the mRNA expression of PTH, but not PTHrP, was moderately increased in the ACC sample compared to NCI H295R cells. Upon tumor resection, serum calcium levels swiftly normalized indicating the tumor as the sole source of PTH secretion. Despite initiation of adjuvant mitotane- and salvage chemo-therapy, the patient died 3 months later upon of a massive tumor relapse with a recurrence of severe hypercalcemia. Conclusion: This case demonstrates paraneoplastic hypercalcemia in a PTH producing ACC. PTH may induce hypercalcemia, impair adrenal steroid synthesis and act as an autocrine growth factor in ACC, as described in few individual cases for PTHrp producing ACC [1]. This suggests a poor prognosis for this rare entity. 1. Rizk-Rabin, M., et al., Differential Expression of Parathyroid Hormone-Related Protein in Adrenocortical Tumors: Autocrine/Paracrine Effects on the Growth and Signaling Pathways in H295R Cells. 2008.

Expression and Prognostic Significance of Neurotrophins and Their Receptors in Canine Mammary Tumors

2020 ◽  
Vol 57 (4) ◽  
pp. 507-519
Author(s):  
Bernadette Rogez ◽  
Quentin Pascal ◽  
Audrey Bobillier ◽  
François Machuron ◽  
Robert-Alain Toillon ◽  
...  
Keyword(s):  
Biological Effects ◽  
Prognostic Significance ◽  
Mammary Tumors ◽  
Clinicopathological Parameters ◽  
Lymph Node Status ◽  
Mammary Carcinomas ◽  
Canine Mammary Tumors ◽  
Common Receptor ◽  
Specific Receptors

Accumulating data highlight the role of neurotrophins and their receptors in human breast cancer. This family includes nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), both synthetized as proneurotrophins (proNGF and proBDNF). (pro)NGF and (pro)BDNF initiate their biological effects by binding to both their specific receptors TrkA and TrkB, respectively, and the common receptor p75NTR. Currently, no data are available about their expression and potential role in canine mammary tumors. The aim of this study was to investigate expression of proNGF and BDNF as well as their receptors TrkA, TrkB, and p75NTR in canine mammary carcinomas, and to correlate them with clinicopathological parameters (grade, histological type, lymph node status, recurrence, and distant metastasis) and survival. Immunohistochemistry was performed on serial sections of 96 canine mammary carcinomas with antibodies against proNGF, BDNF, TrkA, TrkB, and p75NTR. Of the 96 carcinomas, proNGF expression was detected in 71 (74%), BDNF in 79 (82%), TrkA in 94 (98%), TrkB in 35 (37%), and p75NTR in 44 (46%). No association was observed between proNGF, BDNF, or TrkA expression and either clinicopathological parameters or survival. TrkB and p75NTR expression were associated with favorable clinicopathological parameters as well as better overall survival.

scholarly journals PKM2 in Canine Mammary Tumors: Parallels to Human Breast Cancer

2020 ◽  
Vol 70 (4) ◽  
pp. 349-354
Author(s):  
Hyo-Ju Lee ◽  
Hyo-Jeong Han ◽  
Ji-Young Lee ◽  
Woo-Chan Son
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Aerobic Glycolysis ◽  
Prognostic Significance ◽  
Tumor Grade ◽  
Mammary Tumors ◽  
Neoplastic Disease ◽  
Human Breast ◽  
Rate Limiting Step ◽  
Canine Mammary Tumors

PKM2 is a pyruvate kinase isoform that is the final and rate-limiting step in aerobic glycolysis in tumor cells. Increased expression of PKM2 has been detected in human cancers. The present study examined the expression of PKM2 in canine mammary tumors and assessed its prognostic significance. Paraffin sections of 5 adenomas, 67 carcinomas, and 5 samples of nonneoplastic hyperplasia from 77 dogs, aged 8 to 18 y, were evaluated. Significantly higher levels of PKM2 were detected among the carcinomas compared with all other tissues examined. The level of PKM2 expression in carcinoma tissue correlated positively with the tumor grade. These findings suggest that PKM2 may have a similar role in canine mammary tumors to its role in human breast cancer. As such, canine mammary tumors may be useful models for studies focused on the progression of human neoplastic disease.

scholarly journals Comparison of Histology and Clinical Variables to DNA Ploidy in Canine Mammary Tumors

1988 ◽  
Vol 25 (3) ◽  
pp. 219-226 ◽  
Author(s):  
E. Hellmén ◽  
A. Lindgren ◽  
F. Linell ◽  
P. Matsson ◽  
A. Nilsson
Keyword(s):  
Dna Analysis ◽  
Dna Ploidy ◽  
Mammary Tumors ◽  
Clinical Staging ◽  
Benign Tumors ◽  
Aneuploid Cell ◽  
Dna Index ◽  
Regional Lymph Nodes ◽  
Canine Mammary Tumors ◽  
Significant Difference

Flow cytometric DNA analysis was done on 132 canine mammary tumors from 99 dogs to evaluate the relation to histology and to clinical staging. Seventy-one tumors (54%) were histologically malignant; 38 (54%) of these were aneuploid and 33 (46%) were diploid. Fifty-two (39%) tumors were histologically benign, of which 45 (87%) were diploid and seven (13%) aneuploid. There were nine dysplastic mammae (7%); two were aneuploid and the rest diploid. DNA indices varied from 0.72 to 2.35. Of 58 mammary carcinomas, 25 (43%) were diploid and 33 (57%) were aneuploid (of the latter, 16 showed hypodiploidy and 17 hyperdiploidy with a predominance between DNA index 1.10 and 1.50). Three tumors (two carcinomas and one malignant mixed tumor) were multiploid with two aneuploid cell populations. The histological type varied within eight tumors, and in four of these the DNA index also varied. DNA indices varied within three tumors with uniform morphology. No correlation was found between DNA index and age of the dogs, nor between DNA index and tumor size. No significant differences were found between DNA index and histology, tumor growth pattern, or tumor location. Benign tumors were smaller than carcinomas, which were smaller than malignant mesenchymal tumors. Tumors growing adherent to the skin were larger than those not adherent to the skin. The regional lymph nodes were examined in 33 cases. No significant difference between the mean DNA index and presence of lymph node metastasis was found. These results show the possibility of using flow cytometry for DNA analysis in canine mammary tumors. Further investigations are needed to evaluate DNA ploidy as a diagnostic and prognostic tool in the investigation of canine mammary tumors.

Receptor tyrosine kinase gene amplification is predictive of intraoperative seizures during glioma resection with functional mapping

2020 ◽  
Vol 132 (4) ◽  
pp. 1017-1023 ◽  
Author(s):  
Bryan D. Choi ◽  
Daniel K. Lee ◽  
Jimmy C. Yang ◽  
Caroline M. Ayinon ◽  
Christine K. Lee ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Univariate Analysis ◽  
Tumor Resection ◽  
Tumor Grade ◽  
Molecular Data ◽  
Genetic Alterations ◽  
Functional Mapping ◽  
Chi Square ◽  
Kinase Gene ◽  
Glioma Resection

OBJECTIVEIntraoperative seizures during craniotomy with functional mapping is a common complication that impedes optimal tumor resection and results in significant morbidity. The relationship between genetic mutations in gliomas and the incidence of intraoperative seizures has not been well characterized. Here, the authors performed a retrospective study of patients treated at their institution over the last 12 years to determine whether molecular data can be used to predict the incidence of this complication.METHODSThe authors queried their institutional database for patients with brain tumors who underwent resection with intraoperative functional mapping between 2005 and 2017. Basic clinicopathological characteristics, including the status of the following genes, were recorded: IDH1/2, PIK3CA, BRAF, KRAS, AKT1, EGFR, PDGFRA, MET, MGMT, and 1p/19q. Relationships between gene alterations and intraoperative seizures were evaluated using chi-square and two-sample t-test univariate analysis. When considering multiple predictive factors, a logistic multivariate approach was taken.RESULTSOverall, 416 patients met criteria for inclusion; of these patients, 98 (24%) experienced an intraoperative seizure. Patients with a history of preoperative seizure and those treated with antiepileptic drugs prior to surgery were less likely to have intraoperative seizures (history: OR 0.61 [95% CI 0.38–0.96], chi-square = 4.65, p = 0.03; AED load: OR 0.46 [95% CI 0.26–0.80], chi-square = 7.64, p = 0.01). In a univariate analysis of genetic markers, amplification of genes encoding receptor tyrosine kinases (RTKs) was specifically identified as a positive predictor of seizures (OR 5.47 [95% CI 1.22–24.47], chi-square = 5.98, p = 0.01). In multivariate analyses considering RTK status, AED use, and either 2007 WHO tumor grade or modern 2016 WHO tumor groups, the authors found that amplification of the RTK proto-oncogene, MET, was most predictive of intraoperative seizure (p < 0.05).CONCLUSIONSThis study describes a previously unreported association between genetic alterations in RTKs and the occurrence of intraoperative seizures during glioma resection with functional mapping. Future models estimating intraoperative seizure risk may be enhanced by inclusion of genetic criteria.

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