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 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.

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

2000 ◽  
Vol 37 (3) ◽  
pp. 239-247 ◽  
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.

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 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.

Clinicopathological and Prognostic Significance of p27 Expression in Oral Squamous Cell Carcinoma: A Meta-Analysis

2013 ◽  
Vol 28 (4) ◽  
pp. 329-335 ◽  
Author(s):  
Ling Gao ◽  
Wanjie Gu ◽  
Jingjing Zheng ◽  
Wenhao Ren ◽  
Su'e Chang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Publication Bias ◽  
Squamous Cell ◽  
Meta Analysis ◽  
Clinicopathological Parameters ◽  
Lymph Node Status

Despite being already known that p27 can regulate cell proliferation, cell motility and apoptosis, the role of p27 expression in oral squamous cell carcinoma (OSCC) remains controversial. The purpose of this study was to comprehensively evaluate, with a meta-analysis, the clinicopathological and prognostic role of p27 expression in OSCC. A meta-analysis of eligible studies was performed to assess the effects of p27 expression on clinicopathological parameters and overall survival (OS) in patients with OSCC, using pooled relative risks with 95% confidence intervals. Heterogeneity and publication bias were also assessed. Fourteen studies involving a total of 1,010 patients met the inclusion criteria. Low p27 expression was significantly associated with advanced TNM stage (p<0.001), worse histology (p=0.025), and lymph node metastasis (p<0.001), but not with tumor size (p=0.181). The pooled RR of 0.743 (p=0.002) suggested that low p27 expression has a poor prognosis in patients with OSCC. A significant heterogeneity among studies was detected for lymph node status (χ2=34.60, I2=68.2%, p<0.001) and OS (χ2=14.86, I2=39.4%, p=0.095). We did not detect a significant publication bias in this meta-analysis. Our meta-analysis suggests that p27 expression status might be useful as a predictive biomarker in clinical practice, and might potently predict OS in OSCC patients.

scholarly journals Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

2021 ◽  
Vol 22 (6) ◽  
pp. 2870
Author(s):  
Tsung-Chieh Lin ◽  
Michael Hsiao
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Leptin Receptor ◽  
Biological Effects ◽  
Prognostic Significance ◽  
Cell Types ◽  
Receptor Expression ◽  
Specific Cell ◽  
Signaling Axis

Leptin is an obesity-associated adipokine that is known to regulate energy metabolism and reproduction and to control appetite via the leptin receptor. Recent work has identified specific cell types other than adipocytes that harbor leptin and leptin receptor expression, particularly in cancers and tumor microenvironments, and characterized the role of this signaling axis in cancer progression. Furthermore, the prognostic significance of leptin in various types of cancer and the ability to noninvasively detect leptin levels in serum samples have attracted attention for potential clinical applications. Emerging findings have demonstrated the direct and indirect biological effects of leptin in regulating cancer proliferation, metastasis, angiogenesis and chemoresistance, warranting the exploration of the underlying molecular mechanisms to develop a novel therapeutic strategy. In this review article, we summarize and integrate transcriptome and clinical data from cancer patients together with the recent findings related to the leptin signaling axis in the aforementioned malignant phenotypes. In addition, a comprehensive analysis of leptin and leptin receptor distribution in a pancancer panel and in individual cell types of specific organs at the single-cell level is presented, identifying those sites that are prone to leptin-mediated tumorigenesis. Our results shed light on the role of leptin in cancer and provide guidance and potential directions for further research for scientists in this field.

scholarly journals Clinical significance and prognostic role of tumor-associated macrophages infiltration according to histologic location in canine mammary carcinomas

2019 ◽  
Author(s):  
Lidianne Narducci Monteiro ◽  
Diego Carlos dos Reis ◽  
Breno Souza Salgado ◽  
Geovanni Cassali
Keyword(s):  
Vascular Invasion ◽  
Clinical Stage ◽  
Mammary Tumors ◽  
Nodal Metastasis ◽  
Prognostic Indicators ◽  
Tumor Associated Macrophages ◽  
Canine Mammary Tumors ◽  
Prognostic Importance ◽  
Invasive Carcinomas

Abstract Background: Tumor-associated macrophages (TAMs) have been involved in growth and metastases of human and canine mammary tumors. However, the prognostic importance of TAM specific location in canine mammary tumors (CMT) was not evaluated. In this study we evaluated the potential role of TAMs in specific histologic locations – intratumoral (iTAM) and stromal (sTAM), as well as total macrophage (tTAM) counts – as prognostic indicators in CMT. Results: Clinico-pathologic data from 66 animals with mammary carcinoma and their tumors were used in this study. Samples were stained with anti-macrophage antibody for subsequent TAM count. High levels of iTAM, sTAM, and tTAM were related with clinical stage and vascular invasion. Additionally, tTAM alone revealed a relation with tumor size, while high levels of sTAM and tTAM also were correlated with node metastasis and a poor prognosis based on survival analysis. Conclusions: CMT with aggressive features can reveal higher TAM counts. TAMs are associated with vascular invasion and nodal metastasis, and sTAM and tTAM counts are correlated with overall survival, consequently leading to the conclusion that sTAM and/or tTAM counts could be used as prognostic indicators in canine mammary invasive carcinomas.

CD44 expression and regulation during mammary gland development and function

2000 ◽  
Vol 113 (14) ◽  
pp. 2619-2630
Author(s):  
L. Hebbard ◽  
A. Steffen ◽  
V. Zawadzki ◽  
C. Fieber ◽  
N. Howells ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Mammary Tumors ◽  
Mammary Glands ◽  
Mammary Epithelial ◽  
Epithelial Cell Line ◽  
Mammary Carcinomas ◽  
Cd44v6 Expression

The CD44v6 epitope has been widely reported to be expressed in human mammary carcinomas, yet its prognostic significance is controversial and its function in mammary tumors and mammary glands is unknown. To begin to resolve these issues, we analysed in detail the normal postnatal expression patterns and regulation of the CD44v6 epitope in murine mammary glands. We demonstrate that significant CD44v6 epitope expression is first seen during puberty, and that after puberty CD44v6 epitope expression follows the estrous cycle. CD44v6 epitope expression is observed in the myoepithelium and also less widely in luminal epithelial cells. During lactation, CD44v6 epitope expression is turned off and reappears during involution. The CD44 variant isoform bearing the v6 epitope is CD44v1-v10. Using HC11, a mammary epithelial cell line with stem cell characteristics, and facilitated by the cloning of the murine CD44 promoter, we show that growth factors and hormones which regulate ductal growth and differentiation modulate CD44 transcription. Together our data suggest that the CD44v6 epitope is expressed in mammary epithelial stems cells and in lineages derived from these cells, and that CD44v6 expression is regulated in part by hormones and growth factors such as IGF-1 and EGF which regulate the growth and differentiation of the mammary epithelium. The function of these same growth factors and hormones is often perturbed in mammary carcinomas, and we suggest that CD44v6 expression in tumors reflects this perturbation. We conclude that the expression of the CD44v6 epitope observed in some mammary tumors reflects the stem cell origin of breast tumors, and that whether or not the CD44v6 epitope is expressed in a mammary tumor is determined by the differentiation status of the tumor cells.

scholarly journals Prognostic Factors in Canine Mammary Tumors: A Multivariate Study of 202 Consecutive Cases

1993 ◽  
Vol 30 (1) ◽  
pp. 20-27 ◽  
Author(s):  
E. Hellmén ◽  
R. Bergström ◽  
L. Holmberg ◽  
I.-B. Spångberg ◽  
K. Hansson ◽  
...  
Keyword(s):  
Lymph Node ◽  
Tumor Size ◽  
Dna Ploidy ◽  
Univariate Analysis ◽  
Significant Risk ◽  
Mammary Tumors ◽  
S Phase ◽  
Lymph Node Status ◽  
Flow Cytometric ◽  
Canine Mammary Tumors

The prognostic variables of 223 consecutively sampled spontaneous mammary tumors from female dogs were studied. These variables included flow cytometric DNA analysis and cell proliferation measured as cells in S-phase rate evaluated from DNA histograms. The dogs were surgically treated, in most cases with unilateral mastectomy (all mammary glands), and 202 of the 223 dogs were studied temporally following surgery. Univariate analysis with correction for age indicated that the variables of lymph node metastasis, elevated S-phase rate, presence of a sarcoma, DNA aneuploidy, and ulceration and infiltrative growth into underlying tissue had a statistically significant negative influence on the survival rates of dogs with a diagnosed malignant tumor. Similar results were obtained from tests on all dogs, but tumor size and its relative hazard increased with increasing size of the tumors, regardless of whether total or disease-specific mortality was considered. Using multivariate-analysisconducted Cox's proportional hazards model, elevated S-phase rate, increased age, and presence of a sarcoma remained statistically significant risk factors. The prognostic value of DNA ploidy and lymph node status varied depending on choice of end point. The study of tumor growth pattern and tumor size provided no prognostic information in the multivariate analysis. Flow cytometric cell analysis, including S-phase rate and DNA ploidy, is of value in predicting the prognosis of canine mammary tumors and can be used as a new prognostic tool to improve the preoperative diagnostics of canine mammary tumors.

scholarly journals The role of SET/I2PP2A in canine mammary tumors

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Satoru Kake ◽  
Shunya Tsuji ◽  
Shuhei Enjoji ◽  
Sayaka Hanasaki ◽  
Hiroshi Hayase ◽  
...  
Keyword(s):  
Mammary Tumors ◽  
Canine Mammary Tumors
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