Abstract
Background: In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values.
Methods: Samples of malignant and non-cancer autologous reference tissue were collected from 415 breast cancer patients. The tissue samples were cut and either paraffin-embedded or homogenized in a lysis buffer to extract the proteins. HER2 was measured using both immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) and ADVIA Centaur. Phosphorylated HER2 and EGFR (pHER2, pEGFR), total EGFR and the ligands: epidermal growth factor (EGF), transforming growth factor-α (TGFα), amphiregulin (AREG), heparin-binding EGF-like growth factor (HB-EGF), betacellulin (BTC) and epiregulin (EREG) were measured using the Luminex.
Results: The HER2 positivity rate was determined to be 25.2% by the Centaur method vs. 15.8% by IHC and FISH. HER2, HB-EGF, TGFα and AREG were upregulated in cancer tissue as compared with autologous reference tissue while EGFR, pEGFR and EGF were downregulated (p<10–6). pEGFR in autologous reference tissue was negatively correlated to the number of positive lymph nodes and to the tumor size (p=0.0007 and p=0.001, respectively) and furthermore, decreased in the group of mastectomy operated patients as compared with the lumpectomy group (p<10–6). HB-EGF in cancer tissue was positively associated with high grade tumors (p<10–6) and pHER2, HB-EGF and BTC were associated with poor disease free survival (p=0.017, p=0.012 and p=0.0026, respectively).
Conclusions: Our study demonstrated a profound activation of the EGFR system. HB-EGF was increased by factor 10 in cancer tissue and related to the biological aggressiveness of the tumors, and pHER2, HB-EGF and BTC were associated with poor clinical outcome.
©2012 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Masthead
- Masthead
- Editorials
- Cancer epigenomics: moving slowly, but at a steady pace from laboratory bench to clinical practice
- Laboratory networking and sample quality: a still relevant issue for patient safety
- Reviews
- DNA methylation biomarkers and their utility for solid cancer diagnostics
- DNA methylation biomarkers in biological fluids for early detection of respiratory tract cancer
- Global DNA hypomethylation in cancer: review of validated methods and clinical significance
- Genetics and Molecular Diagnostics
- δ0-Thalassemia in cis of βKnossos globin gene: first homozygous description in thalassemia intermedia Libyans and first combination with codon 39 (C→T) in thalassemia intermedia Tunisian patients
- Genetic-based reference values for angiotensin-converting enzyme (ACE) according to I/D polymorphism in a Spanish population sample
- General Clinical Chemistry and Laboratory Medicine
- Effects of sample transportation on commonly requested laboratory tests
- Long-term (in)stability of folate and vitamin B12 in human serum
- Information comparison of the effects of drugs on laboratory tests in drug labels and Young’s book
- First evaluation of Capillarys 2 Flex Piercing® (Sebia) as a new analyzer for HbA1c assay by capillary electrophoresis
- Antioxidant and oligonutrient status, distribution of amino acids, muscle damage, inflammation, and evaluation of renal function in elite rugby players
- Validation of the body fluid module on the new Sysmex XN-1000 for counting blood cells in cerebrospinal fluid and other body fluids
- Measuring Rivaroxaban in a clinical laboratory setting, using common coagulation assays, Xa inhibition and thrombin generation
- Cancer Diagnostics
- Increased concentrations of growth factors and activation of the EGFR system in breast cancer
- Infectious Diseases
- Incidence and significance of elevated lactate in the identification of critically ill patients
- Cardiovascular Diseases
- Lipoprotein-associated phospholipase A2 is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis
- Diabetes
- Serum cystatin C as a marker for early detection of chronic kidney disease and grade 2 nephropathy in Japanese patients with type 2 diabetes
- Letters to the Editor
- Establishing professional phlebotomist group for quality control of the preanalytic variables of clinical laboratory
- Application of quality specification based on biological variation in planning quality control strategy
- Analytical and clinical evaluation of a new immunoassay for therapeutic drug monitoring of infliximab and adalimumab
- Comparison of relationships between FT4 and log TSH in Access DXI 800 Unicel, Modular E170 and ADVIA Centaur XP Analyzer
- Assay-specific pitfalls of catecholamine HPLC assays
- Evaluation of automated nucleated red blood cells counting on Sysmex XE5000 and Siemens ADVIA 2120
- Evaluation of the immature myeloid information (IMI) by Sysmex XE 2100® hematology analyzer in the identification of blasts of myeloid lineage
- Congress Abstracts
- Congress of Laboratory Medicine and Clinical Chemistry / 4th Annual Meeting of the Austrian Society for Laboratory Medicine and Clinical Chemistry (ÖGLMKC)
- Abstracts of the 2012 Convocation of Experts on Laboratory Quality / Embracing the Need of Continued Vigilance to Assure Quality Outcomes in the Modern Laboratory
Articles in the same Issue
- Masthead
- Masthead
- Editorials
- Cancer epigenomics: moving slowly, but at a steady pace from laboratory bench to clinical practice
- Laboratory networking and sample quality: a still relevant issue for patient safety
- Reviews
- DNA methylation biomarkers and their utility for solid cancer diagnostics
- DNA methylation biomarkers in biological fluids for early detection of respiratory tract cancer
- Global DNA hypomethylation in cancer: review of validated methods and clinical significance
- Genetics and Molecular Diagnostics
- δ0-Thalassemia in cis of βKnossos globin gene: first homozygous description in thalassemia intermedia Libyans and first combination with codon 39 (C→T) in thalassemia intermedia Tunisian patients
- Genetic-based reference values for angiotensin-converting enzyme (ACE) according to I/D polymorphism in a Spanish population sample
- General Clinical Chemistry and Laboratory Medicine
- Effects of sample transportation on commonly requested laboratory tests
- Long-term (in)stability of folate and vitamin B12 in human serum
- Information comparison of the effects of drugs on laboratory tests in drug labels and Young’s book
- First evaluation of Capillarys 2 Flex Piercing® (Sebia) as a new analyzer for HbA1c assay by capillary electrophoresis
- Antioxidant and oligonutrient status, distribution of amino acids, muscle damage, inflammation, and evaluation of renal function in elite rugby players
- Validation of the body fluid module on the new Sysmex XN-1000 for counting blood cells in cerebrospinal fluid and other body fluids
- Measuring Rivaroxaban in a clinical laboratory setting, using common coagulation assays, Xa inhibition and thrombin generation
- Cancer Diagnostics
- Increased concentrations of growth factors and activation of the EGFR system in breast cancer
- Infectious Diseases
- Incidence and significance of elevated lactate in the identification of critically ill patients
- Cardiovascular Diseases
- Lipoprotein-associated phospholipase A2 is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis
- Diabetes
- Serum cystatin C as a marker for early detection of chronic kidney disease and grade 2 nephropathy in Japanese patients with type 2 diabetes
- Letters to the Editor
- Establishing professional phlebotomist group for quality control of the preanalytic variables of clinical laboratory
- Application of quality specification based on biological variation in planning quality control strategy
- Analytical and clinical evaluation of a new immunoassay for therapeutic drug monitoring of infliximab and adalimumab
- Comparison of relationships between FT4 and log TSH in Access DXI 800 Unicel, Modular E170 and ADVIA Centaur XP Analyzer
- Assay-specific pitfalls of catecholamine HPLC assays
- Evaluation of automated nucleated red blood cells counting on Sysmex XE5000 and Siemens ADVIA 2120
- Evaluation of the immature myeloid information (IMI) by Sysmex XE 2100® hematology analyzer in the identification of blasts of myeloid lineage
- Congress Abstracts
- Congress of Laboratory Medicine and Clinical Chemistry / 4th Annual Meeting of the Austrian Society for Laboratory Medicine and Clinical Chemistry (ÖGLMKC)
- Abstracts of the 2012 Convocation of Experts on Laboratory Quality / Embracing the Need of Continued Vigilance to Assure Quality Outcomes in the Modern Laboratory