Prognostic value of the human antigen R (HuR) in human breast cancer: high level predicts a favourable prognosis (original) (raw)
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Cytoplasmic HuR Expression Is a Prognostic Factor in Invasive Ductal Breast Carcinoma
HuR is a ubiquitously expressed mRNA-binding protein. Intracellular localization of HuR is predominantly nuclear, but it shuttles between the nucleus and the cytoplasm. In the cytoplasm it can stabilize certain transcripts. Because nucleocytoplasmic translocation of HuR is necessary for its activity, it was hypothesized that cytoplasmic HuR expression in cancer cells could be a prognostic marker. To test the significance of HuR in carcinogenesis of the breast, we have investigated HuR expression in a mouse mammary gland tumor model and from 133 invasive ductal breast carcinoma specimens. HuR expression was elevated in the cyclooxygenase-2 transgene-induced mouse mammary tumors, and its expression was predominantly cytoplasmic in the tumor cells. In the human carcinoma samples, high cytoplasmic immunoreactivity for HuR was found in 29% (38 of 133) of the cases. Cytoplasmic HuR expression associated with high grade (P = 0.0050) and tumor size over 2 cm (P = 0.0082). Five-year distant disease-free survival rate was 42% [95% confidence interval (95% CI), 26-58] in cytoplasm-high category and 84% (95% CI, 76-91) in cytoplasm-negative or -low category (P < < 0.0001), and high cytoplasmic expression of HuR was an independent prognostic factor in a Cox multivariate model (relative risk 2.07; 95% CI, 1.05-4.07). Moreover, high cytoplasmic HuR immunopositivity was significantly associated with poor outcome in the subgroup of node-negative breast cancer in a univariate analysis (P < < 0.0007). Our results show that high cytoplasmic HuR expression is associated with a poor histologic differentiation, large tumor size, and poor survival in ductal breast carcinoma. Thus, HuR is the first mRNA stability protein of which expression associates with poor outcome in breast cancer.
Pathology oncology research : POR, 2017
Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. High HuR expression was positively associated with larger tumor size and advanced disease stage (p = 0.0234 and p = 0.0361, respectively), being more frequently observed in ER negative cases (p = 0.0208). High COX-2 exp...
Relationship between the expression of various markers and prognostic factors in breast cancer
Acta Histochemica, 2005
The immunohistochemical detection of six markers of breast cancer has been compared in the present study with known prognostic factors of the disease to establish locally a standard panel of markers for the management of breast cancer. Sections of tissue of 114 consecutive breast cancer cases were studied immunohistochemically, using antibodies against oestrogen receptor (ER), progesterone receptor (PR), androgen receptor, c-erbB2, cathepsin D, and cyclin D. Marker labelling was graded as recommended in the literature. Using the w 2-test, relationships were determined between marker labelling and histological type of cancer, tumour grade, tumour size, axillary lymph node status and age of patient. A p value below 0.05 was considered significant. A positive relationship was found between ER and PR and lower grades of cancer, and a negative relationship was found with medullary and atypical medullary carcinoma. The four other markers showed no relationship with grade or type of cancer. All markers showed no significant relationship with size of tumour, presence of axillary node metastasis or age of patient. There was positive correlation between c-erbB2 and cathepsin D. Our study confirms the association between ER and PR and histological type and grade of breast cancer, both known parameters of good prognosis. We found no consistent relationship between the other four markers and prognostic factors studied, other than the suggestion that c-erbB2 and cathepsin D may be useful markers for poor prognosis and can be usefully applied locally, especially in the light of the current availability of trastuzumab (Herceptin) for management of c-erbB2-positive cases. We found no relationship between the markers and tumour size, axillary lymph node status or age.
International Journal of Clinical and Diagnostic Pathology, 2021
Background: Prognosis of breast cancer and success of therapeutic interventions largely rely on clinico-pathologic and biological characteristics of tumor and vary due to the heterogenous nature of breast cancers. This study was intended to find correlation between the expression of Estrogen receptor (ER), Progesterone receptor (PR) and Human Epidermal Growth Factor Receptor-2 (HER-2/neu) with histological grade in case of carcinoma of breast. Material and Method: This study was conducted on 56 histologically confirmed specimens of breast carcinoma in Department of Pathology, Surat Municipal Institute of Medical Education and Research. Results: Maximum number of cases of breast carcinoma were found in 41-50 years aged females. Invasive ductal carcinoma-not otherwise specified (IDC-NOS) (82.14%) was most common histological type. Most of the carcinoma showed grade II (62.5%). ER, PR and HER-2/neu positivity was 50%, 42.86% and 42.86% respectively. Conclusion: Evaluation of ER, PR and HER-2/neu status and tumor grade should be incorporated routinely as a part of histopathological reports in all cases of breast carcinoma as they not only help in histopathologic assessment of prognosis, but also help in deciding the management thereby improving overall survival.
Evaluation of Immunohistochemical Profile of Breast Cancer for Prognostics and Therapeutic Use
Nigerian journal of surgery : official publication of the Nigerian Surgical Research Society
Breast cancer is leading cancer in women, and the incidence of breast cancer in India is on the rise. The most common histologic type of breast cancer is infiltrating ductal carcinoma. Prognostic and predictive factors are used in the management of breast cancer. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2/neu) are immunohistochemical markers of prognosis as well as predictors of response to therapy. The study was conducted to evaluate ER, PR, and HER2/neu expressions in invasive ductal carcinomas of the breast by immunohistochemistry, to explore the correlation of these markers to each other and to various clinicopathological parameters: age of the patient, histological grade, tumor size, and lymph node metastasis. This prospective study was conducted on 100 cases of infiltrating ductal carcinoma. Slides were prepared from blocks containing cancer tissue, and immunohistochemical staining was done for ER, PR, and HER2/neu ex...
Asian Pacific journal of health sciences, 2022
Background: Breast carcinoma is the most common malignancy in female worldwide, leading cause of death in women. Immunohistochemistry plays a very important role in the prognostication and treatment determination of breast carcinoma patients. Objective: The objective of the study was to analyze the immunohistochemical markers in invasive carcinoma of breast and to correlate the expression of hormonal receptors with age of the patient, tumor size, histological grade, and lymph node metastasis. Materials and Methods: The study was conducted on 88 infiltrating ductal breast carcinoma sample in a tertiary care hospital of Southern Assam for a period of 2 year (January2018-December 2019). Data including age, tumor size, and histologic grade and lymph node status retrieved from pathology department. Chi-square was used to determine the statistical significance between estrogen receptors and progesterone receptors (ER/PR) status human epidermal receptor growth factor 2 (HER2/neu) status along with their correlation with various clinicopathological parameters with respect to infiltrating ductal breast carcinoma. Result: The mean age of the patients was 56.6 years. We observed correlation between ER and PR expression with age, tumor size, and tumor grade. There was correlation between HER2/neu expression and age only. None of the markers showed correlation with lymph node involvement (P > 0.05). Conclusion: Our findings showed the importance of biomarkers (ER, PR, and HER2/neu) expression as prognostic factors for therapeutic decision.
A predictive and prognostic biomarker profile of carcinoma breast
IP innovative publication pvt ltd , 2020
Context: The immunohistochemical (IHC 4) biomarker profile is part of the standard histopathology report of all newly diagnosed and recurrent cases of carcinoma Breast. This profile is the basis for all neoadjuvant and adjuvant treatment planning in these cases. Aims: 1. To study the IHC4 biomarker profile of Carcinoma Breast cases at our Institute. 2. To study the correlation of the five types of molecular subgroups with various clinical and histological parameters. Settings and Design: 271 cases of carcinoma breast diagnosed and treated at our Institute, during the period 1st July 2017 till 30th June 2018. This is a prospective, observational study. Materials and Methods: All the cases of biopsy proven carcinoma Breast were subjected to immunohistochemical staining for four markers- ER, PR, Her 2, and Ki 67. Fo rmalin Fixed Paraffin Embedded tumor tissue was stained for 4 biomarkers and scored with appropriate method. (Interpretive Guide: ASCO - CAP Test Guidelines Recommendations 2013) Manual method of staining was employed, using commercially available reagents. The cases were classified into five molecular subtypes. Results: Triple negative breast carcinoma was the most frequent subgroup, followed by the luminal B and A types and the Her2 enriched cases were lowest in number. A few cases showed triple positive staining pattern. Conclusions: The IHC 4 biomarker findings in every case of carcinoma has a direct impact on the treatment decision making and also on risk stratification of the patients.
Neoplasia, 2016
Hu-antigen R (HuR) is an RNA-binding post-transcriptional regulator that belongs to the Hu/ELAV family. HuR expression levels are modulated by a variety of proteins, microRNAs, chemical compounds or the microenvironment and in turn HuR affects mRNA stability and translation of various genes implicated in breast cancer formation, progression, metastasis and treatment. The aim of the present review is to critically summarise the role of HuR in breast cancer development and its potential as a prognosticator and a therapeutic target. In this aspect, all the existing English literature concerning HuR expression and function in breast cancer cell lines, in vivo animal models and clinical studies is critically presented and summarized. HuR modulates many genes implicated in biological processes crucial for breast cancer formation, growth and metastasis, while the link between HuR and these processes has been demonstrated directly in vitro and in vivo. Additionally, clinical studies reveal that HuR is associated with more aggressive forms of breast cancer and is a putative prognosticator for patients' survival. All the above indicate HuR as a promising drug target for cancer therapy; nevertheless, additional studies are required to fully understand its potential and determine against which types of breast cancer and at which stage of the disease a therapeutic agent targeting HuR would be more effective.
Expression of 6 Common Antigenic Markers in Invasive Ductal Breast Carcinoma
Applied Immunohistochemistry & Molecular Morphology, 2011
Expression of estrogen (ER) and progesterone receptors, c-erbB-2 oncogene, mutant p53 antioncogene (mp53), e-cadherin adhesion, and apoptotic caspase-8 antigens in tumor relative to matched normal tissue specimens from 102 unselected patients with primary ductal breast carcinoma of various tumor grades was assessed by immunohistochemistry and correlated with patient's biologic and clinical features, such as age, menstrual status, age of menarche, tumor grade and diameter, the presence or absence of metastases, and number of infiltrated lymph nodes. We observed association of e-cadherin adhesion, ER and progesterone antigen marker expression with low histologic grade tumors and limited number of lymph node metastases and of c-erbB-2, mp53, and casp-8 antigen marker expression with high histologic grade tumors and increased number of lymph node metastases. We also observed strong correlation (P<0.05) between 4 of the 6 biomarkers and 4 of the 7 patient/tumor parameters examined. Our findings support the hypothesis of independent expression of these 4 strong biomarkers and reveal that nearly 40% of all breast tumor cases studied express similar proportions of 2 major phenotypic combinations [ER/c-erbB-2/mp53/casp-8: +/+/ À /+ (19.6%) & +/ À / À /+ (17.8%)]. We conclude that, in agreement with earlier reports, our findings support the diagnostic and potential prognostic value of these markers in the clinical assessment of breast cancer.