scholarly journals Immunohistochemical Analysis of Na+/K+-ATPase and Bone Morphogenetic Protein-2 Expressions in Both Parenchymal and Stromal Cells from Benign and Malignant Canine Mammary Tumors

Author(s):  
ozlem ozmen

Abstract Canine mammary tumors are the most common type of dog tumor, and they are similar to human breast tumors. Na+/K+-ATPase is a common plasma membrane ion pump with important physiological and pathophysiological functions. In mammary tumors, the tumor microenvironment was composed of a heterogeneous population of tumor cells and nearby endogenous stromal cells. Bone morphogenetic proteins (BMPs) regulate fetal development, tissue homeostasis and differentiation, and a variety of cellular functions. The purpose of this study is to examine the immunohistochemical expression of Na+/K+-ATPase and BMP-2 in tumoral and stromal cells from benign and malignant canine mammary tumors. In this study, ten benign and ten malignant mammary tumors from the archives of the Department of Pathology were used, with five normal breast tissues serving as controls. The results of the revealed that tumors had higher levels of Na+/K+-ATPase and BMP-2 expressions than normal mammary tissue. While both markers were expressed negatively or mildly in benign tumors, they increased significantly in malignant tumors. Both Na+/K+-ATPase and BMP-2 are expressed by tumoral and stromal cells in canine mammary tumors. When compared to compared to BMP-2, Na+/K+-ATPase expression was found to be more severe. This study found that Na+/K+-ATPase and BMP-2 can be used as markers of malignancy in canine mammary tumors and that stromal cells also play an important role in tumor progression. These findings also indicated that Na+/K+-ATPase and BMP-2 may be used for early diagnosis or as a potential target for treatment of canine and human breast tumors in the future.

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Leena Rajathy Port Louis ◽  
Khub Chandra Varshney ◽  
Madhavan Gopalakrishnan Nair

Steroid hormones are found to play a major role in the genesis and progression of mammary tumors. The aim of this study was to immunohistochemically detect the presence of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and progesterone receptor (PR) and also to study the association between these markers in 29 cases of benign (11) and malignant (18) canine mammary tumors. ERα immunostaining was noticed in only one case of carcinosarcoma specifically in the nuclei of epithelial and a few myoepithelial cells. ERβ immunostaining was noticed in the nuclei and cytoplasm of epithelial cells and smooth muscles lining the blood vessels. Immunoexpression of ERβ was 82% in benign tumors and 78% in malignant tumors. PR immunostaining was expressed in the nuclei of epithelial cells in both benign and malignant tumors. Among the 15 PR+ cases, 6 (55%) were of benign type, and 9 (50%) were of malignant type. The most common group of hormone receptor was the ERα−/PR+/ERβ+ (46%) in benign tumors and ERα−/PR−/ERβ+ (38%) in malignant tumors. Although there was no significant association between ERα and PR with ERβ, the findings indicated that ERβ was consistently expressed in both benign and malignant tumors, irrespective of ERα and PR status.


2018 ◽  
Vol 56 (2) ◽  
pp. 208-219 ◽  
Author(s):  
Ana Canadas ◽  
Miguel França ◽  
Cristina Pereira ◽  
Raquel Vilaça ◽  
Hugo Vilhena ◽  
...  

Histopathology remains the cornerstone for diagnosing canine mammary tumors (CMTs). Recently, 2 classification systems (the World Health Organization [WHO] classification of 1999 and the proposal of 2011) and 2 grading methods based on the human Nottingham grade have been used by pathologists. Despite some evidence that the histological subtype and grade are prognostic factors, there is no comprehensive comparative study of these classification and grading systems in the same series of CMTs. In this study, the 2 classifications and the 2 grading methods were simultaneously applied to a cohort of 134 female dogs with CMTs. In 85 animals with malignant tumors, univariable and multivariable survival analyses were performed. Using the 2 systems, the proportion of benign (161/305, 53%) and malignant (144/305, 47%) tumors was similar and no significant differences existed in categorization of benign tumors. However, the 2011 classification subdivided malignant tumors in more categories—namely, those classified as complex, solid, and tubulopapillary carcinomas by the WHO system. Histological subtype according to both systems was significantly associated with survival. Carcinomas arising in benign tumors, complex carcinomas, and mixed carcinomas were associated with a better prognosis. In contrast, carcinosarcomas and comedocarcinomas had a high risk of tumor-related death. Slight differences existed between the 2 grading methods, and grade was related to survival only in univariable analysis. In this cohort, age, completeness of surgical margins, and 2 index formulas adapted from human breast cancer studies (including tumor size, grade, and vascular/lymph node invasion) were independent prognostic factors.


Author(s):  
M. P. Patel ◽  
D. J. Ghodasara ◽  
S. H. Raval ◽  
B. P. Joshi

The aim of present investigation was to study the gross morphology and incidence of canine mammary tumors (CMTs) based on age, sex, breed, reproductive status and location along with histopathological classification and immunohistochemical characteristics. A total of 56 CMTs samples were collected from 49 cases of dogs. Gross morphology was studied in 26 cases of canine mammary tumors. For histopathological classification, samples were fixed in 10% formalin, embedded in paraffin and sections (5 μm thick) obtained from each was stained with HandE stain. Immuno-histochemistry was carried out by using p63 antibody to confirm the histopathological types of CMTs. Malignant tumors and benign tumors were mostly observed in older dogs. Among 9 breeds affected, the highest incidence was recorded in a German shepherd. Caudal abdominal pair was most commonly affected. Most of the cases were observed in intact female dogs, except for one male dog. The tumors were oval and round in shape with 30–2000 g weight, soft to hard in consistency and grayish white cut surface. Out of 56 CMTs, the highest incidence was found of malignant neoplasms (36/56, 64.28%), followed by benign neoplasms (10/56, 17.85%) and non-neoplastic proliferation hyperplasia/dysplasia (10/56, 17.85%). Complex carcinoma, carcinoma, and malignant myoepithelioma and malignant myoepithelioma were confirmed by p63 antibody. In these neoplasms, myoepithelial cells showed strong immunoreactivity with p63.


2010 ◽  
Vol 62 (6) ◽  
pp. 1348-1351 ◽  
Author(s):  
G.E Lavalle ◽  
A.C Bertagnolli ◽  
W.L.F Tavares ◽  
M.A.N.D Ferreira ◽  
G.D Cassali

The correlation between microvessel density and mast cells density in canine mammary tumors was studied. Sixty-five samples of canine mammary tumors, being 24 benign and 41 malignant, were analyzed. The routine Toluidine Blue staining method was used to assess the mast cells. To evaluate angiogenesis, the immunohistochemical expression of CD31 was assessed. There was no significant difference in either mast cells (P=0.44) or microvessel density (P=0.77) between malignant and benign tumors. A positive correlation was observed between microvessel density and mast cells (r=0.39; P=0.011) in malignant tumors. These results suggest that mast cells may play a role in canine mammary malignant tumors development, promoting angiogenesis, similar to some tumors described in the human species


1996 ◽  
Vol 33 (5) ◽  
pp. 527-532 ◽  
Author(s):  
M. BratuliĆ ◽  
Ž GrabareviĆ ◽  
B. ArtukoviĆ ◽  
D. Capak

Twenty-eight canine mammary tumors were evaluated for histopathologic classification as recommended by the World Health Organization and silver-binding nucleolar organizer region (AgNOR) and nucleolus counts. Samples of surgically excised tumors and tumors taken at necropsy were fixed in neutral formalin, embedded in paraffin, and cut into 1-3-μm-thick sections. Two sections were taken from each tumor: one was stained with hematoxylin and eosin and the other was treated with the silver staining technique for the demonstration of AgNORs. After histopathologic classification, the number of nucleoli and the number of AgNORs/nucleus and AgNORs/nucleolus were determined. Statistical analysis (Student's t-test) showed a significant difference in the mean number of nucleoli ( P < 0.005), mean number of AgNORs/nucleolus ( P < 0.001), and mean number of AgNORs/nucleus ( P < 0.005) between benign and malignant canine mammary tumors. There was no significant differences between metastatic and nonmetastatic malignant tumors.


Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1687
Author(s):  
Giovanni P. Burrai ◽  
Andrea Gabrieli ◽  
Valentina Moccia ◽  
Valentina Zappulli ◽  
Ilaria Porcellato ◽  
...  

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.


2003 ◽  
Vol 40 (2) ◽  
pp. 207-212 ◽  
Author(s):  
M. Doré ◽  
I. Lanthier ◽  
J. Sirois

Mammary tumors are the most common neoplasms in female dogs. Induction of cyclooxygenase-2 (COX-2) has been implicated in various cancers in humans. However, expression of COX-2 has not been investigated in canine mammary tumors. Normal mammary gland ( n = 4), simple or complex adenomas ( n = 63), and simple or complex adenocarcinomas ( n = 84) were studied by immunohistochemistry. Results showed that COX-2 was not expressed in the normal gland but was detected in 24% of adenomas and in 56% of adenocarcinomas ( P < 0.001). The incidence of COX-2 expression and the intensity of the COX-2 signal were higher in adenocarcinomas than in adenomas ( P < 0.001). These results demonstrate for the first time that COX-2 is induced in a proportion of canine mammary tumors and that COX-2 expression is more frequent and more intense in malignant than in benign tumors, suggesting a potential role for COX-2 in canine mammary tumorigenesis.


2012 ◽  
Vol 23 (20) ◽  
pp. 4097-4108 ◽  
Author(s):  
KangAe Lee ◽  
Qike K. Chen ◽  
Cecillia Lui ◽  
Magdalena A. Cichon ◽  
Derek C. Radisky ◽  
...  

Epithelial–mesenchymal transition (EMT) is a form of epithelial plasticity implicated in fibrosis and tumor metastasis. Here we show that the mechanical rigidity of the microenvironment plays a pivotal role in the promotion of EMT by controlling the subcellular localization and downstream signaling of Rac GTPases. Soft substrata, with compliances comparable to that of normal mammary tissue, are protective against EMT, whereas stiffer substrata, with compliances characteristic of breast tumors, promote EMT. Rac1b, a highly activated splice variant of Rac1 found in tumors, localizes to the plasma membrane in cells cultured on stiff substrata or in collagen-rich regions of human breast tumors. At the membrane, Rac1b forms a complex with NADPH oxidase and promotes the production of reactive oxygen species, expression of Snail, and activation of the EMT program. In contrast, soft microenvironments inhibit the membrane localization of Rac1b and subsequent redox changes. These results reveal a novel mechanotransduction pathway in the regulation of epithelial plasticity via EMT.


2000 ◽  
Vol 37 (3) ◽  
pp. 239-247 ◽  
Author(s):  
A. Nieto ◽  
L. Peña ◽  
M. D. Pérez-Alenza ◽  
M. A. Sánchez ◽  
J. M. Flores ◽  
...  

Eighty-nine canine mammary tumors and dysplasias of 66 bitches were investigated to determine the immunohistochemical expression of classical estrogen receptor (ER-α) and its clinical and pathologic associations and prognostic value. A complete clinical examination was performed and reproductive history was evaluated. After surgery, all animals were followed-up for 18 months, with clinical examinations every 3–4 months. ER-α expression was higher in tumors of genitally intact and young bitches ( P < 0.01, P < 0.01) and in animals with regular estrous periods ( P = 0.03). Malignant tumors of the bitches with a previous clinical history of pseudopregnancy expressed significantly more ER-α ( P = 0.04). Immunoexpression of ER-α decreased significantly with tumor size ( P = 0.05) and skin ulceration ( P = 0.01). Low levels of ER-α were significantly associated with lymph node involvement ( P < 0.01). Malignant tumors had lower ER-α expression than did benign tumors ( P < 0.01). Proliferation index measured by proliferating cell nuclear antigen immunostaining was inversely correlated with ER-α scores ( P = 0.05) in all tumors. Low ER-α levels in primary malignant tumors were significantly associated with the occurrence of metastases in the follow-up ( P = 0.03). Multivariate analyses were performed to determine the prognostic significance of some follow-up variables. ER-α value, Ki-67 index, and age were independent factors that could predict disease-free survival. Lymph node status, age, and ER-α index were independent prognostic factors for the overall survival. The immunohistochemical detection of ER-α in canine mammary tumors is a simple technique with prognostic value that could be useful in selecting appropriate hormonal therapy.


Author(s):  
C. N Neeraja ◽  
S. R. Voleti ◽  
D. Subrahmanyam ◽  
K. Surekha ◽  
P. Raghuveer Rao

The aim of present investigation was to study the gross morphology and incidence of canine mammary tumors (CMTs) based on age, sex, breed, reproductive status and location along with histopathological classification and immunohistochemical characteristics. A total of 56 CMTs samples were collected from 49 cases of dogs. Gross morphology was studied in 26 cases of canine mammary tumors. For histopathological classification, samples were fixed in 10% formalin, embedded in paraffin and sections (5 μm thick) obtained from each was stained with HandE stain. Immuno-histochemistry was carried out by using p63 antibody to confirm the histopathological types of CMTs. Malignant tumors and benign tumors were mostly observed in older dogs. Among 9 breeds affected, the highest incidence was recorded in a German shepherd. Caudal abdominal pair was most commonly affected. Most of the cases were observed in intact female dogs, except for one male dog. The tumors were oval and round in shape with 30–2000 g weight, soft to hard in consistency and grayish white cut surface. Out of 56 CMTs, the highest incidence was found of malignant neoplasms (36/56, 64.28%), followed by benign neoplasms (10/56, 17.85%) and non-neoplastic proliferation hyperplasia/dysplasia (10/56, 17.85%). Complex carcinoma, carcinoma, and malignant myoepithelioma and malignant myoepithelioma were confirmed by p63 antibody. In these neoplasms, myoepithelial cells showed strong immunoreactivity with p63.Development of nitrogen use efficient (NUE) rice varieties is inevitable for sustainability of environmental friendly and economical agricultural practices. Several management practices are being studied for increasing efficiency of spatial and temporal inputs of N under National Innovations for Climate Resilient Agriculture (NICRA). Attempts are being made to develop NUE rice varieties with multidisciplinary approach and conventional selection along with mapping and next generation sequencing strategies. Around 800 rice genotypes were characterized under low and recommended nitrogen for two consecutive seasons and the promising donors further evaluated to identify consistent NUE rice genotypes. Several mapping populations were developed using the NUE donors and popular rice varieties. QTL/genomic regions were identified for yield under low N using biparental and association mapping. Using minimum marker set of 50 rice SSR markers, 12 genomic regions were identified for yield and yield associated traits under low nitrogen. Several promising recombinants of yield and NUE were identified and these breeding lines were evaluated under multi-locations and stable performers were identified under AICRIP Trial - Evaluation of Radiation and Nitrogen use efficient promising rice genotypes -Plant Physiology during Kharif 2016, 2017 and 2018. As nitrogen is the building block of biomass, an optimum N is required for realizing the yield. The strategy should be to maximise uptake and improve utilization, so that remobilization of N to yield is achieved under low N.


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