Prognostic impact of alterations in E-cadherin and P-cadherin expression in canine mammary tumors

Expression of cadherins has been correlated to the development and aggressiveness of epithelial neoplasms, however, in canine mammary tumors, their significance prognostic is uncertain. Due to this fact, the expression of the intracellular adhesion molecules E and P-cadherin and correlation with overall survival were analyzed in 25 canine mammary gland tumors. E-cadherin expression reduction was correlated with histological type, high histological grade, and overall survival rate. P-cadherin staining was higher in malignant tumors, unrelated to other clinicopathological features of aggressiveness. The results of this study suggest a relationship between lower expression of E and P-cadherin and worse prognostic in canine mammary tumors, including shorter overall survival.

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CD44 and CD24 Expression and Prognostic Significance in Canine Mammary Tumors

Veterinary Pathology ◽

10.1177/0300985818813653 ◽

2018 ◽

Vol 56 (3) ◽

pp. 377-388 ◽

Cited By ~ 3

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.

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Number of Nucleoli and Nucleolar Organizer Regions per Nucleus and Nucleolus — Prognostic Value in Canine Mammary Tumors

Veterinary Pathology ◽

10.1177/030098589603300507 ◽

1996 ◽

Vol 33 (5) ◽

pp. 527-532 ◽

Cited By ~ 10

Author(s):

M. BratuliĆ ◽

Ž GrabareviĆ ◽

B. ArtukoviĆ ◽

D. Capak

Keyword(s):

Malignant Tumors ◽

Organizer Region ◽

Nucleolar Organizer Region ◽

Nucleolar Organizer ◽

Staining Technique ◽

Mammary Tumors ◽

World Health ◽

Nucleolar Organizer Regions ◽

Canine Mammary Tumors ◽

Significant Difference

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.

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Diagnostic efficacy of smear cytology and Robinson’s cytological grading of canine mammary tumors with respect to histopathology, cytomorphometry, metastases and overall survival

PLoS ONE ◽

10.1371/journal.pone.0191595 ◽

2018 ◽

Vol 13 (1) ◽

pp. e0191595 ◽

Cited By ~ 2

Author(s):

Izabella Dolka ◽

Michał Czopowicz ◽

Anna Gruk-Jurka ◽

Agata Wojtkowska ◽

Rafał Sapierzyński ◽

...

Keyword(s):

Overall Survival ◽

Mammary Tumors ◽

Diagnostic Efficacy ◽

Canine Mammary Tumors

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

Animals ◽

10.3390/ani10091687 ◽

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.

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An Immunohistochemical Study on the Expression of Sex Steroid Receptors in Canine Mammary Tumors

ISRN Veterinary Science ◽

10.5402/2012/378607 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Leena Rajathy Port Louis ◽

Khub Chandra Varshney ◽

Madhavan Gopalakrishnan Nair

Keyword(s):

Estrogen Receptor ◽

Epithelial Cells ◽

Estrogen Receptor Alpha ◽

Malignant Tumors ◽

Steroid Receptors ◽

Estrogen Receptor Beta ◽

Smooth Muscles ◽

Mammary Tumors ◽

Benign Tumors ◽

Canine Mammary Tumors

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.

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Retrospective Study of Mammary Lesions in Bitches - Uberlândia, MG, Brazil

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.80788 ◽

2017 ◽

Vol 45 (1) ◽

pp. 8

Author(s):

Mariana Batista Andrade ◽

Ednaldo Carvalho Guimarães ◽

Arlinda Flores Coleto ◽

Nicolle Pereira Soares ◽

Alessandra Aparecida Medeiros-Ronchi

Keyword(s):

Retrospective Study ◽

Tumor Size ◽

Hormone Receptors ◽

Malignant Tumors ◽

Histological Grade ◽

Mammary Tumors ◽

Mammary Glands ◽

Malignant Neoplasms ◽

The Mean ◽

Inguinal Glands

Background: Mammary tumors are a type of neoplasia that are most commonly found in female dogs and are mostly malignant. The aim of this study, performed in the Laboratory of Veterinary Pathology of the Federal University of Uberlândia (LVP-FUU) from 2004 to 2014, was to determine the prevalence of mammary tumors in bitches and to verify the relationship between the epidemiological factors (age and breed) and clinicopathological aspects (ulceration, tumor size, and malignancy) in the occurrence of tumors.Materials, Methods & Results: A retrospective study was carried out using histopathological information retrieved from the LPV-UFU database. We collected the information on age and breed of female dogs, as well as about the location, macroscopic aspects, and histological diagnosis of mammary lesions. Only female dogs were considered for this study; a total of 911 histopathological protocols (with only one diagnosis) were analyzed along with 36 protocols that presented more than one diagnosis of mammary tumor. The age of animals ranged from one to 20 years, and the mean age was 9.99 years. The most affected breeds of dogs were: Cross breed (39.56% - 288/728) and Poodle (20.19% - 147/728). The inguinal glands were most affected by the malignant tumors (P < 0.05). A prevalence of tumors bigger than 5 cm in diameter (T3) was observed in the elderly animals (P = 0.0154) and in the inguinal mammary glands (P = 0.044). Simple carcinoma was the most frequent histological type.Discussion: Research shows that more than 40% of the tumors in bitches are located in the mammary glands, emphasizing the importance of this type of neoplasia in female dogs. Mammary tumors develop more frequently in the middle-aged and elderly bitches, with the highest occurrence being in the age range of 8 and 10 years, corroborating our observation in the present study that the mean age of bitches was 9.99 years. In this survey, a higher incidence was observed in mongrel bitches compared to that in the Poodle breed. Some authors affirm that there is no racial predisposition for the occurrence of this pathology; however, a compilation of data suggests a predisposition of at least 10 breeds, with the involvement of an as yet unidentified genetic component. Of these, six breeds (Poodle, Cocker Spaniel, Pointer, Maltese, Yorkshire Terrier, and Dachshund) were found to be predisposed to mammary tumors in this study. The percentage (49.23%) of malignant tumors found in the inguinal glands is consistent with the findings reported in literature, and might be associated with a greater amount of parenchyma, abundance of hormone receptors in these glands, and vascularization provided by the caudal superficial epigastric artery and vulvar branches of external pudendal artery. Tumor size is considered to be a prognostic factor and tumors ≤ 3 cm in diameter (T1) have a better prognosis. Consequently, the prevalence of tumors ≥ 5 cm in diameter (T3) in elderly animals is probably related to malignancy of the lesions, because tumors usually progress to a worse histological grade with time. The higher occurrence of T3 in inguinal glands might be related to the abundance of parenchyma and/or hormonal receptors in them. As in the present study, data from literature refer to the superiority of malignant histological types, with prevalence varying between 68 and 91%. When prolonged, the time between the onset of tumor and clinical evaluation may be a determinant in the progression from benign to malignant tumors. Among the malignant neoplasms, simple carcinoma was observed to be prevalent, followed by mixed tumors with carcinoma, in agreement with the results of several studies. It is concluded that mammary tumors are more prevalent in older mongrel dogs and Poodle. Attention should be paid to inguinal mammary tumors, because these are mainly malignant.

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Immunohistologic Detection of Estrogen Receptor Alpha in Canine Mammary Tumors: Clinical and Pathologic Associations and Prognostic Significance

Veterinary Pathology ◽

10.1354/vp.37-3-239 ◽

2000 ◽

Vol 37 (3) ◽

pp. 239-247 ◽

Cited By ~ 102

Author(s):

A. Nieto ◽

L. Peña ◽

M. D. Pérez-Alenza ◽

M. A. Sánchez ◽

J. M. Flores ◽

...

Keyword(s):

Estrogen Receptor ◽

Lymph Node ◽

Prognostic Value ◽

Malignant Tumors ◽

Prognostic Significance ◽

Mammary Tumors ◽

Proliferation Index ◽

Lymph Node Status ◽

Canine Mammary Tumors

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.

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Prognostic Impact of lncRNA MCM3AP-AS1 Expression in Malignant Solid Tumors: A Systematic Review and Meta-analysis

10.21203/rs.3.rs-1185329/v1 ◽

2021 ◽

Author(s):

qi le ◽

wei chen ◽

Lei Jiang ◽

Wenwen Hu ◽

Nan Yao

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Malignant Tumors ◽

Meta Analysis ◽

Clinical Stage ◽

Prognostic Impact ◽

China National Knowledge Infrastructure ◽

Poor Overall Survival ◽

Advanced Clinical Stage ◽

High Level

Abstract Objectives: MCM3AP-AS1 is a newly discovered long non-coding RNA that functions as a biomarker in many different cancer types. However, the pooled role of lncRNA MCM3AP-AS1 in the prognosis of human cancers remains unclear. We performed a systematic review and meta-analysis to explore its potential prognosis for malignant tumors. Materials and methods: A literature survey was conducted by searching in the PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang databases for studies published as of September 1, 2021. The pooled hazard ratio (HR) and 95% confidence interval (95% CI) were calculated to evaluate the relationship between MCM3AP-AS1 expression and overall survival (OS). The endpoints also included various clinical parameters. Results: A total of 14 studies containing 921 cancer patients were finally included into this meta-analysis. The results comprehensively showed that increased MCM3AP-AS1 expression was significantly correlated with poor overall survival (HR = 1.83, 95% CI: 1.56-2.14, P<0.00001). A subgroup meta-analysis for overall survival was conducted. Additionally, high level of lncRNA MCM3AP-AS1 was significantly associated with worse differentiation (OR = 1.76, 95 % CI: 1.12–2.75, P = 0.01), larger tumor size (OR = 2.70, 95 % CI: 1.13–6.46, P = 0.03), advanced clinical stage (OR = 2.52, 95 % CI: 1.32–4.81, P = 0.005) and lymph node metastasis (OR = 2.85, 95 % CI: 1.16–7.00, P = 0.02), respectively. Conclusions: LncRNA MCM3AP-AS1 might be a potential and unfavorable prognostic biomarker of cancer.

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Immunohistochemical and molecular expression of laminin-332 gamma-2 chain in canine mammary tumors

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/s0102-09352011000100005 ◽

2011 ◽

Vol 63 (1) ◽

pp. 28-35

Author(s):

D.A.P.C Zuccari ◽

R Castro ◽

B.V Jardim ◽

U.M Mancini ◽

G.M Polachini

Keyword(s):

Western Blot ◽

Mammary Cancer ◽

Malignant Tumors ◽

Mammary Tumors ◽

Malignant Potential ◽

Rt Pcr ◽

Canine Mammary Tumors ◽

Weak Expression ◽

Molecular Expression ◽

Laminin 332

Forty-eight cases of canine mammary cancer were investigated to evaluate the immunohistochemical distribution of the γ2 chain of laminin-332. Tumor cells were compared to a pool of normal mammary tissues using quantitative RT-PCR. The western blot was performed in eight tumor samples as complementary test to evaluate protein integrity. Immunohistochemistry experiments showed negative, focal, and weak expression of laminin-332 γ2 in tumors with the worst prognosis. Quantitative PCR revealed downregulation of the gene in 27 (56.2%) of the animals. Out of the 16 dogs with γ2 chain overexpression, seven were still alive. The western blot results showed bands generation of 36, 50, and 98kDa, suggesting degradation of laminin-332 γ2 in malignant tumors. The results suggest that, in the future, low expression and/or degradation of laminin-332 γ2 chain in canine mammary tumors may be used as an indicator of malignant potential. However, further studies are necessary to corroborate these results

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Canine Mammary Tumors: Comparison of Classification and Grading Methods in a Survival Study

Veterinary Pathology ◽

10.1177/0300985818806968 ◽

2018 ◽

Vol 56 (2) ◽

pp. 208-219 ◽

Cited By ~ 13

Author(s):

Ana Canadas ◽

Miguel França ◽

Cristina Pereira ◽

Raquel Vilaça ◽

Hugo Vilhena ◽

...

Keyword(s):

Prognostic Factors ◽

Malignant Tumors ◽

Mammary Tumors ◽

Classification Systems ◽

World Health ◽

Benign Tumors ◽

Histological Subtype ◽

Canine Mammary Tumors ◽

Nottingham Grade ◽

Health Organization

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.

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