scholarly journals Combined High Resistin and EGFR Expression Predicts a Poor Prognosis in Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yue Zeng ◽  
Chih-Hsin Tang ◽  
Yan Wang ◽  
Hua-Jun Lu ◽  
Bi-Fei Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Molecular Classification ◽  
Breast Cancer Tissue ◽  
Her2 Status ◽  
Cancer Tissue ◽  
Egfr Expression ◽  
Epidermal Growth

Elevated levels of resistin and epidermal growth factor receptor (EGFR) facilitate the development of breast cancer, although there are no reports of any correlation between these proteins. This study analyzed 392 human breast cancer tissue specimens and 42 samples of adjacent normal tissue. Rates of positive and strongly positive resistin expression were significantly higher in breast cancer tissue than in the adjacent nontumor tissue (83.2% vs. 23.8% and 20.9% vs. 0.0%, respectively; P < 0.001 for both comparisons). Positive resistin expression was significantly associated with tumor size, grade, stage, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and molecular classification; strongly positive resistin expression was associated with tumor grade, ER, PR, HER2 status, and molecular classification. Significantly positive correlations were observed between positive and strongly positive resistin expression and corresponding levels of EGFR expression. Relapse-free and overall survival was worse for patients with high levels of both proteins than for those with high levels of only one protein or normal levels of both proteins. Our evidence suggests that combined high levels of resistin and EGFR expression correlate with survival in patients with breast cancer.

scholarly journals Modulation of EGFR Gene Transcription by a Polymorphic Repetitive Sequence – a Link between Genetics and Epigenetics

2000 ◽  
Vol 15 (1) ◽  
pp. 105-110 ◽  
Author(s):  
F. Gebhardt ◽  
H. BÜrger ◽  
B. Brandt
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Model Calculations ◽  
Ca Repeat ◽  
Egfr Gene ◽  
Egfr Expression ◽  
Epidermal Growth

The epidermal growth factor receptor (EGFR) plays a crucial role in growth, differentiation and motility of normal as well as tumor cells. The transduction of extracellular signals to the cytoplasm via the receptor not only depends on ligand binding, but is also determined by the receptor density on the cell surface. Therefore, with regard to cancer diagnosis and therapeutic approaches targeting EGFR it is important to know how the expression level of EGFR is controlled. We found that transcription activity declines with increasing numbers of CA dinucleotides of a highly polymorphic CA repeat in the first intron of the epidermal growth factor receptor gene. In vivo data from cultured cell lines support these findings, although other regulation mechanisms can compensate this effect. In addition, we showed that RNA elongation terminates at a site closely downstream of the simple sequence repeat (SSR) and that there are two separate major transcription start sites. Model calculations for the helical DNA conformation revealed a high bendability in the EGFR polymorphic region, especially if the CA stretch is extended. These data suggest that the CA-SSR can act like a joint, bringing the promoter in proximity to a putative repressor protein bound downstream of the CA-SSR. The data indicate that this polymorphism may be a marker for cancer, linking genetic and epigenetic risk factors. Furthermore, in breast cancer, heterozygous tumors with short CA-SSR showed an elevated EGFR-expression in contrast to tumours with longer CA-SSR. Tumours with loss of heterozygosity in intron 1 of egfr revealed an increased EGFR expression if the longer allele was lost. Moreover, decreased EGFR gene levels were significantly correlated with poor prognosis in breast cancer.

Radioimmunohistochemistry of Epidermal Growth Factor Receptor in Breast Cancer

2002 ◽  
Vol 126 (2) ◽  
pp. 177-181
Author(s):  
Kevin W. Robertson ◽  
Jonathon R. Reeves ◽  
Alison K. Lannigan ◽  
James J. Going ◽  
Timothy G. Cooke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Lines ◽  
Dynamic Range ◽  
Growth Factor Receptor ◽  
Prognostic Indicators ◽  
Egfr Expression ◽  
Epidermal Growth

Abstract Context.—Conflicting reports of epidermal growth factor receptor (EGFR) expression in breast cancer and inconstant relationships with established prognostic indicators and outcomes suggest difficulties with EGFR measurement. Objective.—To compare EGFR measurement in a panel of cell lines and in breast carcinomas by radioimmunohistochemistry (R-IHC), conventional immunohistochemistry (IHC), and a ligand binding (LB) assay. Design.—Eight EGFR-expressing cell lines and 50 primary breast carcinoma specimens were analyzed for EGFR by IHC, R-IHC, and LB assays. A further 153 primary breast cancer specimens were analyzed by R-IHC alone. Results.—All 3 assays were in good agreement for the cell lines. In the subset of the 50 carcinoma specimens, EGFR was detected by LB assays in 19 (38%) and by IHC in 24 (48%). However, R-IHC detected EGFR in 46 (92%) of 50 and in 186 (92%) of all 203 carcinoma specimens. The LB assay agreed poorly with R-IHC of carcinomas, possibly because the LB assay is sensitive to EGFR-expressing nontumor breast parenchyma in the tissue analyzed. Both IHC and R-IHC on carcinoma specimens agreed better, but 26 carcinoma specimens (52%) in which EGFR was not detectable by IHC had a 10-fold range in receptor level detectable by R-IHC. Conclusion.—To elucidate the role of EGFR or other growth factor receptors in breast cancer requires accurate, sensitive receptor assays. With its dynamic range, R-IHC returned meaningful results over the entire range of expression actually present in breast cancer, which LB assays and IHC failed to do.

Effect of Age on Breast Cancer Outcomes in Women With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From a Herceptin Adjuvant Trial

2013 ◽  
Vol 31 (21) ◽  
pp. 2692-2698 ◽  
Author(s):  
Ann H. Partridge ◽  
Shari Gelber ◽  
Martine J. Piccart-Gebhart ◽  
Florine Focant ◽  
Matthew Scullion ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth ◽  
The Impact ◽  
Positive Breast Cancer

Purpose Previous research has suggested that young age at diagnosis is an independent risk factor for breast cancer recurrence and death. No prior studies have adequately controlled for human epidermal growth factor receptor 2 (HER2) status or anti-HER2 treatment. We sought to evaluate whether age was a prognostic or predictive factor in the HERA trial. Patients and Methods We used 2-year median follow-up data and dichotomized age at 40 years to evaluate its prognostic effect on outcomes for women assigned to trastuzumab for 1 year or observation. Results Of the 1,703 women randomly assigned to 1 year of trastuzumab and 1,698 to observation, 722 (21%) were age ≤ 40 years at study entry. In separate Cox models, controlling for relevant prognostic and predictive factors, disease-free (DFS) and overall survival (OS) hazard ratios (HRs) were consistent for women age ≤ 40 versus > 40 years, regardless of treatment assignment (observation group: DFS HR age ≤ 40 v > 40 years, 1.18; 95% CI, 0.90 to 1.54; OS HR age ≤ 40 v > 40 years, 1.01; 95% CI, 0.60 to 1.69; trastuzumab group: DFS HR age ≤ 40 v > 40 years, 1.11; 95% CI, 0.81 to 1.51; OS HR age ≤ 40 v > 40 years, 1.18; 95% CI, 0.66 to 2.09). Interaction between age group and treatment effect was not statistically significant (DFS P = .89; OS P = .55). Conclusion In a retrospective analysis of a large randomized controlled trial of women with early-stage HER2-positive breast cancer, age was not strongly associated with risk of early recurrence or prediction of benefit from trastuzumab therapy. Future research should investigate whether age is a predictor of later recurrence and evaluate the impact of age within groups with other tumor subtypes.

Clinically Used Breast Cancer Markers Such As Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Are Unstable Throughout Tumor Progression

2012 ◽  
Vol 30 (21) ◽  
pp. 2601-2608 ◽  
Author(s):  
Linda Sofie Lindström ◽  
Eva Karlsson ◽  
Ulla M. Wilking ◽  
Ulla Johansson ◽  
Johan Hartman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Tumor Progression ◽  
Patient Management ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Er Positive ◽  
Epidermal Growth

Purpose To investigate whether hormonal receptors and human epidermal growth factor receptor 2 (HER2) change throughout tumor progression, because this may alter patient management. Patients and Methods The study cohort included female patients with breast cancer in the Stockholm health care region who relapsed from January 1, 1997, to December 31, 2007. Either biochemical or immunohistochemical (IHC)/immunocytochemical (ICC) methods were used to determine estrogen receptor (ER), progesterone receptor (PR), and HER2 status, which was then confirmed by fluorescent in situ hybridization for IHC/ICC 2+ and 3+ status. Results ER (459 patients), PR (430 patients), and HER2 (104 patients) from both primary tumor and relapse were assessed, revealing a change in 32.4% (McNemar's test P < .001), 40.7% (P < .001), and 14.5% (P = .44) of patients, respectively. Assessment of ER (119 patients), PR (116 patients), and HER2 (32 patients) with multiple (from two to six) consecutive relapses showed an alteration in 33.6%, 32.0%, and 15.7% of patients, respectively. A statistically significant differential overall survival related to intraindividual ER and PR status in primary tumor and relapse (log-rank P < .001) was noted. In addition, women with ER-positive primary tumors that changed to ER-negative tumors had a significant 48% increased risk of death (hazard ratio, 1.48; 95% CI, 1.08 to 2.05) compared with women with stable ER-positive tumors. Conclusion Patients with breast cancer experience altered hormone receptor and HER2 status throughout tumor progression, possibly influenced by adjuvant therapies, which significantly influences survival. Hence, marker investigations at relapse may potentially improve patient management and survival.

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