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.

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

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
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.

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.

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 The prognostic role of the androgen receptor in patients with triple-negative early breast cancers and primary surgery.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12042-e12042
Author(s):  
Lynn Jongen ◽  
Giuseppe Floris ◽  
Hans Wildiers ◽  
Frank Claessens ◽  
Luna De Sutter ◽  
...  
Keyword(s):  
Lymph Node ◽  
Androgen Receptor ◽  
Adjuvant Chemotherapy ◽  
Protein Expression ◽  
Metastatic Disease ◽  
Odds Ratio ◽  
Prognostic Value ◽  
Triple Negative ◽  
Lymph Node Status

e12042 Background: The prognostic value of androgen receptor (AR) expression in triple-negative breast cancer (TNBC) is debated and might be partially masked by the use of adjuvant chemotherapy, which might benefit AR-negative TNBC more than AR-positive cases. We compared the prognostic value of AR in a case control study of consecutive women with TNBC treated or not with adjuvant chemotherapy (ACT). Methods: We retrospectively studied AR expression by immunohistochemistry in all consecutive patients with a secondary metastatic TNBC treated in UZ-Leuven between 2000 and 2009. The control group were cases of TNBC never developing secondary metastatic disease during a long follow-up period matched 1:1 for age and tumor grade. Relations between demographics and clinical pathological features and AR protein expression were studied, including stromal tumor infiltrating lymphocytes (sTILs). Secondary metastatic disease connections with AR protein expression was assessed using the Akaike information criterion; time-to metastasis (TTM) was studied using a linear model with and without ACT correcting for lymph node involvement. We explored whether results differed by AR protein expression levels (0%, 1-34%, ≥34% of tumor cells) and body-mass index (BMI) comparing normal ( < 25kg/m2) with overweight/obese patients BMI. Results: We included 139 patients (69 metastatic and 70 non-metastatic; median age 51.0 years); median follow-up for both groups was 8 years. AR protein expression level ≥ 1% was observed in 25% (n = 34) and ACT was given in 73% (n = 101). AR-positive as compared to AR-negative TNBC patients were older (p = 0.04). Results based on multivariable models including lymph node status and ACT as confounders showed that AR-negative cases have a higher metastasis risk compared to AR-positive patients (3.015 odds ratio (95% CI 1.199-7.582), p = 0.02); this difference was more significant in ACT-naive patients (10.823 odds ratio (95% CI 1.897-61.740), p = 0.007). ACT-treated patients had the best outcome if AR was low (1≤ and < 34%) followed by those with a normal weight and an AR-negative high sTIL TNBC. Conclusions: The AR is prognostic in TNBC and this is clearer in non-ACT treated patients with a TNBC. Our results might suggest that if ACT is given, only the AR-positive TNBC with low AR-expression do well.

scholarly journals Chromosomal Imbalances are Associated with Metastasis-Free Survival in Breast Cancer Patients

2002 ◽  
Vol 24 (2-3) ◽  
pp. 77-87 ◽  
Author(s):  
Michaela Aubele ◽  
Gert Auer ◽  
Herbert Braselmann ◽  
Jörg Nährig ◽  
Horst Zitzelsberger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Prognostic Value ◽  
Inverse Correlation ◽  
Distant Metastases ◽  
Lymph Node Status ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Chromosomal Imbalances

Multiple chromosomal imbalances have been identified in breast cancer using comparative genomic hybridization (CGH). Their association with the primary tumors' potential for building distant metastases is unknown. In this study we have investigated 39 invasive breast carcinomas with a mean follow‐up period of 99 months (max. 193 months) by CGH to determine the prognostic value of chromosomal gains and losses. The mean number of chromosomal imbalances per tumor was 6.5±0.7 (range 2 to 18). The most frequent alterations identified in more than 1/3 of cases were gains on chromosomes 11q13, 12q24, 16, 17, and 20q, and losses on 2q and 13q. A significantly different frequency of chromosomal aberrations (p≤0.05) was found between DNA‐diploid and non‐diploid tumors (gain on chromosome 17). Differences were also noted between tumors progressing to distant metastases within the period of follow‐up and those which do not (gains on 11q13 and 12q24; loss on 12q). Significant univariate correlations (p≤0.05) with the metastasis‐free survival of patients were found for lymph node status, the cytometrical determined DNA ploidy (diploid/non‐diploid) and anisokaryosis, and for DNA gains on 11q13, 12q24, 17, and 18p. An unexpected inverse correlation was found between clinical outcome and gains on 11q13 and 12q24. In multivariate analysis independent prognostic value, in addition to lymph node status, was found for chromosomal gains on 11q13, 12q24, 17 and 18p. Amplification on 20q, which did not correlate with metastasis‐free survival in a univariate analysis, showed weak prognostic significance in combination with the nodal status. The prognostic value of chromosomal alterations – some of them by inverse correlation – suggests an interaction and/or compensation of the involved amplified genes and their effects on the occurrence of distant metastases in breast cancer patients.

scholarly journals A Prospective Analysis of Immunohistochemically Determined Estrogen Receptor α and Progesterone Receptor Expression and Host and Tumor Factors as Predictors of Disease-free Period in Mammary Tumors of the Dog

2005 ◽  
Vol 42 (2) ◽  
pp. 200-212 ◽  
Author(s):  
J. Martín de las Mulas ◽  
Y. Millán ◽  
R. Dios
Keyword(s):  
Estrogen Receptor ◽  
Lymph Node ◽  
Progesterone Receptor ◽  
Tumor Size ◽  
Prognostic Value ◽  
Malignant Tumors ◽  
Host Factors ◽  
Positive Group ◽  
Histologic Grading ◽  
Disease Free

The immunohistochemically determined estrogen receptor (ER) α (ERα) and progesterone receptor (PR) status, as well as recognized, well-accepted prognostic indicators and host factors were prospectively analyzed in 84 cases of primary canine mammary carcinoma for their effect on disease-free period (recurrence free, metastasis free, or combined) (DFP) after an observation period of 18 months. The presence of one or both receptors, as well as tumor size, lymph node status, histologic grading, intravascular growth, and necrosis, were of prognostic value for DFP. In multivariate analysis, only tumor size and histologic grading proved to be independent prognosticators. None of the host factors analyzed were of prognostic value for DFP. ERα, PR, or both were detected in 173 out of 228 tumors: 70 ERα and PR; 5 ERα only; 98 PR only. Statistically significant differences regarding the presence of one or both receptors were observed between benign and malignant tumors and between complex, mixed, and simple histologic subtypes of benign and malignant tumors. In the group of malignant tumors ( n = 155), the presence of one or both receptors was more frequent in tumors smaller than 3 cm, without lymph node metastasis, with tubulopapillary rather than solid patterns of growth among simple carcinomas, of histologic grades I and II, without both intravascular growth and necrosis, and with lymphocyte cell infiltrates. The most frequent groups of hormone receptors-positive tumors were the ERα-positive and PR-positive group among benign and the ERα-negative and PR-positive group among malignant tumors.

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 Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series

2013 ◽  
Vol 33 (6) ◽  
Author(s):  
Maria Aparecida Azevedo Koike Folgueira ◽  
Simone Maistro ◽  
Maria Lucia Hirata Katayama ◽  
Rosimeire Aparecida Roela ◽  
Fiorita Gonzales Lopes Mundim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Extracellular Matrix ◽  
Lymph Node ◽  
Plasminogen Activator ◽  
Prognostic Significance ◽  
Lymph Node Status ◽  
Positive Staining ◽  
Regional Metastasis ◽  
Extracellular Matrix Components

CAFs (cancer-associated fibroblasts), the most abundant cell type in breast cancer stroma, produce a plethora of chemokines, growth factors and ECM (extracellular matrix) proteins, that may contribute to dissemination and metastasis. Axillary nodes are the first metastatic site in breast cancer; however, to the present date, there is no consensus of which specific proteins, synthesized by CAFs, might be related with lymph node involvement. The purpose of this study was to perform a systematic review of CAF biomarkers associated with the presence of regional metastasis. PubMed was searched using the words: ‘breast cancer’ and ‘lymph node’ and fibroblast or stroma or microenvironment. After exclusions, eight studies evaluating biomarkers immunoexpression in CAFs and lymph node status were selected. Biomarkers evaluated in these studies may be divided in two groups, according to their ontology: extracellular matrix components [MMP13 (matrix metalloproteinase 13), TIMP2 (tissue inhibitor of metalloproteinases-2), THBS1 (thrombospondin 1), LGALS1 (lectin, galactoside-binding, soluble, 1)] and response to wounding [PDPN (podoplanin), PLAU (plasminogen activator, urokinase), PLAUR (plasminogen activator, urokinase receptor), CAV1 (caveolin 1), THBS1, LGALS1]. A positive expression of MMP13 and LGALS1 in CAFs was associated with enhanced OR (odds ratio) for regional metastasis. Contrariwise, CAV1 positive staining of fibroblasts was associated with decreased OR for nodal involvement. Expression of MMP13, PDPN and CAV1 was further tested in a new series of 65 samples of invasive ductal breast carcinomas by immunohistochemistry and no association between biomarkers expression in CAFs and nodal status was found. It was suggested that breast cancer subtypes may differentially affect CAFs behaviour. It would be interesting to evaluate the prognostic significance of these biomarkers in CAFs from different tumour types.

Oncogenes and Male Breast Carcinoma: c-erbB-2 and p53 Coexpression Predicts a Poor Survival

2000 ◽  
Vol 18 (16) ◽  
pp. 2948-2956 ◽  
Author(s):  
Achille Pich ◽  
Elena Margaria ◽  
Luigi Chiusa
Keyword(s):  
Breast Carcinoma ◽  
Prognostic Value ◽  
Ductal Carcinoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Male Breast ◽  
Male Breast Carcinoma ◽  
P53 Immunoreactivity ◽  
Mib 1

PURPOSE: To investigate the prognostic value of biomarkers in male breast carcinoma (MBC). PATIENTS AND METHODS: Fifty patients (mean age, 62.2 years) with invasive ductal carcinoma were retrospectively studied. All patients received surgery; 35 had adjuvant postoperative therapy. The median follow-up was 59 months (range, 1 to 230 months). c-myc, c-erbB-2, p53, and bcl-2 proteins were immunohistochemically detected on sections from formalin-fixed, paraffin-embedded tissues using 9E11, CB11, DO7, and bcl-2 124 monoclonal antibodies (mAbs). Estrogen, progesterone, and androgen receptors were detected using specific mAbs. Cell proliferation was assessed by MIB-1 mAb. RESULTS: In univariate analysis, c-myc, c-erbB-2, and p53 protein overexpression was significantly correlated with prognosis. The median survival was 107 months for c-myc–negative and 52 months for c-myc–positive patients (P = .01), 96 months for c-erbB-2–negative and 39 months for c-erbB-2–positive patients (P = .02), and 100 months for p53-negative and 33 months for p53-positive patients (P = .0008). Tumor histologic grade (P = .01), tumor size (P = .02), patient age at diagnosis (P = .03), and MIB-1 scores (P = .0004) also had prognostic value. In multivariate analysis, only c-erbB-2 and p53 immunoreactivity retained independent prognostic significance. All nine patients who did not express c-erbB-2 and p53 proteins were alive after 58 months, whereas none of the 14 patients expressing both proteins survived at 61 months follow-up (P = .0002). CONCLUSION: Overexpression of c-myc, c-erbB-2, and p53 proteins may be regarded as an additional prognostic factor in MBC. The combination of c-erbB-2 and p53 immunoreactivity can stratify patients into different risk groups.

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