Cellular Proliferative and Telomerase Activity in Canine Mammary Gland Tumors

2000 ◽  
Vol 37 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Y. Funakoshi ◽  
H. Nakayama ◽  
K. Uetsuka ◽  
R. Nishimura ◽  
N. Sasaki ◽  
...  

In canine mammary tumors, we examined the telomerase activity, proliferative activity by proliferative cell nuclear antigen (PCNA) immunohistochemistry, and percentage of apoptotic cells by the deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. The relationship between these measures and histopathologic malignancy was also investigated. PCNA index was highest in malignant tumors (adenocarcinoma: 27.0%; malignant mixed tumor: 15.7%), followed by benign tumors (adenoma: 4.4%; benign mixed tumor: 5.3%), hyperplasia (2.1%), and normal mammary gland (0.9%). In adenoma and adenocarcinoma, papillary and solid types showing higher cellularity tended to have higher PCNA indices than did cystic and tubular types. Although the TUNEL index was <1% in all cases, the relationship between this measure and histopathologic diagnosis showed the same tendency as observed in PCNA immunostaining. Telomerase activity was detectable in all adenomas, benign mixed tumors, and adenocarcinomas examined. In contrast, all normal mammary glands, hyperplasias, and malignant mixed tumors were negative for telomerase. Relative telomerase activity (RTA) of adenocarcinoma (56.5) was significantly higher than that of adenoma (27.8) and benign mixed tumor (33.9), and a significant positive correlation ( P < 0.001) was noted between RTA and PCNA index. No significant correlations were noted between either PCNA or TUNEL index and clinical features such as metastasis and tumor diameter. PCNA index and telomerase activity may be useful markers for judging malignancy of canine mammary tumors.

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.


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.


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.


2017 ◽  
Vol 10 (3) ◽  
pp. 87-99 ◽  
Author(s):  
Geovanni Cassali ◽  
Karine Damasceno ◽  
Angelica Bertagnolli ◽  
Alessandra Estrela-Lima ◽  
Gleidice Lavalle ◽  
...  

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.


2002 ◽  
Vol 39 (2) ◽  
pp. 247-256 ◽  
Author(s):  
A. Espinosa de los Monteros ◽  
M. Y. Millán ◽  
J. Ordás ◽  
L. Carrasco ◽  
C. Reymundo ◽  
...  

The immunohistochemical expression of the smooth muscle-specific protein calponin was studied to assess the contribution of myoepithelial cells to the histogenesis of spindle cells of complex and mixed tumors of the mammary gland of the dog and the origin of cartilage and bone in mixed tumors. Formalin-fixed tissues from 55 benign and malignant tumors (49 also containing surrounding normal mammary gland) were evaluated. Periacinar and periductal myoepithelial cells of all the 49 normal mammary glands were diffusely stained by the anti-human calponin monoclonal antibody. Calponin was found in 53 (98%) of the tumors studied, reacting with the myoepithelium-like cells of 86% of benign tumors and their remnants in 85% of malignant tumors. Five different types of calponin-immunoreactive myoepithelial cells were identified: hypertrophic myoepithelial cells, fusiform cells, stellate myoepithelial cells, rounded (myoepithelial) cells, and chondroblasts. Differences in staining intensity and staining pattern among these five types of cells suggested a transition of myoepithelial cells to chondroblasts. Stromal myofibroblasts also showed calponin immunoreactivity, but they did not react with a cytokeratin 14 monoclonal antibody, which recognizes myoepithelial cells in mammary gland. Calponin appears to be a very sensitive marker of normal and neoplastic myoepithelium in the canine mammary gland, and its identification in different cell types of complex and mixed tumors of the mammary gland of the dog suggests a major histogenetic role for myoepithelial cells.


2007 ◽  
Vol 59 (5) ◽  
pp. 1163-1168 ◽  
Author(s):  
G.D. Cassali ◽  
A. Salvador ◽  
C. Freitas ◽  
A.P. Dutra ◽  
F.C. Schmitt

Flow cytometric analysis of DNA content was performed on 28 samples of canine mammary tumors. Nine of them were benign and 19 were malignant. All benign tumors and 11 malignant tumors (57.9%) were diploid (P<0.05). Form the aneuploid tumors, five (26.3%) were hyperdiploid, one (5.3%) hypodiploid, one (5.3%) near triploid and one (5.3%) multiploid. The analysis of the expression of the markers PR and CD31 revealed a significant difference between diploid and aneuploid tumors (P<0.05). The immunoreactivity of PR was higher in diploid tumors, while the immunoreactivity of CD31 was stronger in aneuploid tumors. No difference between the markers MIB-1, c-erbB2, p53 and Cyclin D1 was observed (P>0.05). Using the flow cytometry analysis and immunohistochemistry, it was found a close relationship between aneuploidy and malignant character of neoplasias, progesterone receptor (PR) negative immunostaining and higher microvases density. No correlation between DNA content and S phase or immunoreactivity for the markers MIB-1, p53, c-erbB2 and Cyclin D1 was observed.


2001 ◽  
Vol 38 (6) ◽  
pp. 703-709 ◽  
Author(s):  
S. Tateyama ◽  
K. Uchida ◽  
T. Hidaka ◽  
M. Hirao ◽  
R. Yamaguchi

Seventy-three mammary tumors and three mammary tissue specimens were examined to elucidate the expression of bone morphogenetic protein (BMP)-6 in the myoepithelial cells of canine mammary gland tumors. Morphologically, the myoepithelial cells were classified into four types: resting and proliferating cells inside the basement membrane, and spindle- and star-shaped cells proliferating in the outer area of the basement membrane. The characteristics of these myoepithelial cells were confirmed by immunohistochemistry using antibodies raised against keratin, cytokeratin 19, alpha-smooth muscle actin, and vimentin. In simple adenoma, a small number of resting myoepithelial cells was immunopositive for BMP-6. In complex adenomas and benign mixed tumors, all types of myoepithelial cells, depending in some cases on their specific location within the tumor, were immunopositive for BMP-6, but almost all of the tubular epithelial cells were immunonegative. Foci consisting of a proliferation of BMP-6–positive star- and spindle-shaped cells had mucinous stroma with marked hyaline and chondroid changes. In contrast, the foci with BMP-6–negative spindle- and star-shaped cells tended to have mucinous stroma without chondroid change. Several types of mesenchymal cells including chondrocytes, osteoblasts, and fibroblastlike cells in the mixed tumors, showed an intense immunopositive reaction for the BMP-6 antibody, and were located close to the ectopic cartilage and bone matrix. No significant immunoreactivity for BMP-6 was observed in most of the malignant mammary tumors; only one malignant mixed tumor was examined. All of these findings indicate that BMP-6 expression in myoepithelial cells may increase in complex adenomas and benign mixed tumors in canine mammary glands, and that BMP-6 expression is most intense in the vicinity of chondroid matrix in these tumors.


2011 ◽  
Vol 14 (2) ◽  
pp. 245-251 ◽  
Author(s):  
I. Dolka ◽  
T. Motyl ◽  
E. Malicka ◽  
R. Sapierzyński ◽  
M. Fabisiak

Relationship between receptors for insulin-like growth factor - I, steroid hormones and apoptosis-associated proteins in canine mammary tumors In the veterinary literature there are few data concerning the expression of insulin-like growth factor type I (IGF-IR) in the canine mammary gland tumors. The aim of the present study was the evaluation of IGF-IR expression and its correlation to the expression of estrogen receptor α (ERα) and progesterone receptor (PR), proteins: Bcl-2, Bax, p53 in canine mammary gland tumors, and also a correlation with other features: bitch's age, tumor diameter, histologic type of tumor, degree of histologic malignancy, proliferate activity. The study was done on 112 epithelial neoplasms: 21 (19%) were adenoma, 38 (34%) complex carcinoma (adenocarcinoma), 47 (42%) simple carcinoma (adenocarcinoma) and 6 (5%) solid carcinoma. Histochemistry and immunohistochemistry methods were employed. It was shown that more common and/or higher IGF-IR expression in cells of canine mammary gland tumors was related to the histologic type of cancer of worse prognostic (solid and simple carcinoma), high histologic degree of malignancy (III°) but the statistical analysis did not reveal any significant differences. We observed the high degree of IGF-IR expression in tumors which displayed the high ERα and PR expression. These results suggest the involvement of IGF-IR in the development of hormonosensitive canine mammary tumors. Additionally, the significant positive correlation between expression of IGF-IR and p53, Bax was found. Our study provides some evidence that interactions exist between the IGF-IR and these apoptosis-associated proteins may contribute to the development and progression of canine mammary gland tumors. These results require further investigations.


2021 ◽  
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.


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