HER-2 protein concentrations in breast cancer cells increase before immunohistochemical and fluorescence in situ hybridization analysis turn positive
-
Dorte A. Olsen
Abstract
Background: The level of HER-2/neu in breast cancer cells is normally measured by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). It determines whether patients should be treated with trastuzumab (Herceptin®). In this study, HER-2 protein in breast cancer tissue was measured using a quantitative method.
Methods: Tissue samples of malignant and adjacent benign breast tissue were collected from 118 consecutive women admitted for surgical treatment of breast cancer. The HER-2 protein concentration was determined by 2 HER-2 assays: ELISA and the Bayer ADVIA Centaur assay. Paraffin-embedded tissue sections of the corresponding tumors were analyzed by IHC and FISH.
Results: Increased HER-2 concentrations in cancer tissue were found compared to autologous reference tissue (p<0.0001, Wilcoxon test) and normal breast tissue (p<0.0001, Mann-Whitney test). Good concordance rates were observed between the methods: 95.8% for IHC and FISH; 86.4% for IHC and ELISA; and 87.3% for FISH and ELISA. The HER-2 positivity rate was determined to 26.3% by ELISA, 12.7% by IHC and 16.9% by FISH. No correlation was found with tumor grade, axillary node status or serum HER-2 levels.
Conclusions: Detection of HER-2 overexpression by measuring HER-2 in tissue extracts by ELISA seems to be more sensitive than IHC and FISH. This suggests that some patients deprived of Herceptin treatment may benefit from this treatment and may also explain the conversion phenomenon from HER-2-negative to HER-2-positive observed in relapse and metastatic disease.
Clin Chem Lab Med 2007;45:177–82.
References
1. Pauletti G, Godolphin W, Press MF, Slamon DJ. Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene1996;13:63–72.Search in Google Scholar
2. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science1987;235:177–82.10.1126/science.3798106Search in Google Scholar
3. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science1989;244:707–12.10.1126/science.2470152Search in Google Scholar
4. Ravdin PM, Chamness GC. The c-erbB-2 proto-oncogene as a prognostic and predictive marker in breast cancer: a paradigm for the development of other macromolecular markers – a review. Gene1995;159:19–27.10.1016/0378-1119(94)00866-QSearch in Google Scholar
5. Seshadri R, Firgaira FA, Horsfall DJ, McCaul K, Setlur V, Kitchen P. Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group. J Clin Oncol1993;11:1936–42.10.1200/JCO.1993.11.10.1936Search in Google Scholar
6. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med2001;344:783–92.10.1056/NEJM200103153441101Search in Google Scholar
7. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol2002;20:719–26.10.1200/JCO.2002.20.3.719Search in Google Scholar
8. Press MF, Bernstein L, Thomas PA, Meisner LF, Zhou JY, Ma Y, et al. HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol1997;15:2894–904.10.1200/JCO.1997.15.8.2894Search in Google Scholar
9. Gjerdrum LM, Sorensen BS, Kjeldsen E, Sorensen FB, Nexo E, Hamilton-Dutoit S. Real-time quantitative PCR of microdissected paraffin-embedded breast carcinoma: an alternative method for HER-2/neu analysis. J Mol Diagn2004;6:42–51.10.1016/S1525-1578(10)60490-4Search in Google Scholar
10. Merkelbach-Bruse S, Wardelmann E, Behrens P, Losen I, Buettner R, Friedrichs N. Current diagnostic methods of HER-2/neu detection in breast cancer with special regard to real-time PCR. Am J Surg Pathol2003;27:1565–70.10.1097/00000478-200312000-00010Search in Google Scholar PubMed
11. Dittadi R, Catozzi L, Gion M, Brazzale A, Capitanio G, Gelli MC, et al. Comparison between western blotting, immunohistochemical and ELISA assay for p185neu quantitation in breast cancer specimens. Anticancer Res1993;13:1821–4.Search in Google Scholar
12. Dittadi R, Donisi PM, Brazzale A, Marconato R, Spina M, Gion M. Immunoenzymatic assay of erbB2 protein in cancer and non-malignant breast tissue. Relationships with clinical and biochemical parameters. Anticancer Res1992;12:2005–10.Search in Google Scholar
13. Konecny G, Untch M, Arboleda J, Wilson C, Kahlert S, Boettcher B, et al. Her-2/neu and urokinase-type plasminogen activator and its inhibitor in breast cancer. Clin Cancer Res2001;7:2448–57.Search in Google Scholar
14. Muller V, Thomssen C, Karakas C, Eustermann I, Ramirez PJ, Coith C, et al. Quantitative assessment of HER-2/neu protein concentration in breast cancer by enzyme-linked immunosorbent assay. Int J Biol Markers2003;18:13–20.10.1177/172460080301800103Search in Google Scholar
15. Valeron PF, Chirino R, Fernandez L, Torres S, Navarro D, Aguiar J, et al. Validation of a differential PCR and an ELISA procedure in studying HER-2/neu status in breast cancer. Int J Cancer1996;65:129–33.10.1002/(SICI)1097-0215(19960117)65:2<129::AID-IJC1>3.0.CO;2-0Search in Google Scholar
16. Valeron PF, Chirino R, Vega V, Falcon O, Rivero JF, Torres S, et al. Quantitative analysis of p185(HER-2/neu) protein in breast cancer and its association with other prognostic factors. Int J Cancer1997;74:175–9.10.1002/(SICI)1097-0215(19970422)74:2<175::AID-IJC6>3.0.CO;2-WSearch in Google Scholar
17. Lamy PJ, Nanni I, Fina F, Bibeau F, Romain S, Dussert C, et al. Reliability and discriminant validity of HER2 gene quantification and chromosome 17 aneusomy analysis by real-time PCR in primary breast cancer. Int J Biol Markers2006;21:20–9.10.5301/JBM.2008.1088Search in Google Scholar
18. Eppenberger-Castori S, Kueng W, Benz C, Caduff R, Varga Z, Bannwart F, et al. Prognostic and predictive significance of ErbB-2 breast tumor levels measured by enzyme immunoassay. J Clin Oncol2001;19:645–56.10.1200/JCO.2001.19.3.645Search in Google Scholar
19. Gancberg D, Di Leo A, Cardoso F, Rouas G, Pedrocchi M, Paesmans M, et al. Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol2002;13:1036–43.10.1093/annonc/mdf252Search in Google Scholar
20. Carney WP. HER2 status is an important biomarker in guiding personalized HER-2 therapy. Personalized Medicine2005;2:317–24.10.2217/17410541.2.4.317Search in Google Scholar
21. Kong SY, Nam BH, Lee KS, Kwon Y, Lee ES, Seong MW, et al. Predicting tissue HER2 status using serum HER2 levels in patients with metastatic breast cancer. Clin Chem2006;52:1510–5.10.1373/clinchem.2006.067512Search in Google Scholar
22. Carney WP, Neumann R, Lipton A, Leitzel K, Ali S, Price CP. Potential clinical utility of serum HER-2/neu oncoprotein concentrations in patients with breast cancer. Clin Chem2003;49:1579–98.10.1373/49.10.1579Search in Google Scholar
23. Rohan TE, Hartwick W, Miller AB, Kandel RA. Immunohistochemical detection of c-erbB-2 and p53 in benign breast disease and breast cancer risk. J Natl Cancer Inst1998;90:1262–9.10.1093/jnci/90.17.1262Search in Google Scholar
24. Stark A, Hulka BS, Joens S, Novotny D, Thor AD, Wold LE, et al. HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer. J Clin Oncol2000;18:267–74.10.1200/JCO.2000.18.2.267Search in Google Scholar
©2007 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Associations between folate, vitamin B12, homocysteine and pathologies related to aging: the need to consider complex nutrient-nutrient and gene-nutrient interactions and the functional and socio-economic determinants in population-based studies
- Hyperhomocysteinemia and cardiovascular risk in postmenopausal women: the role of folate supplementation
- Association of vitamin B12, folate and homocysteine with functional and pathological characteristics of the elderly in a mountainous village in Sicily
- Association of thyroid dysfunction with vitamin B12, folate and plasma homocysteine levels in the elderly: a population-based study in Sicily
- Desmond (Des) Kenny MSc MCB FICI FRCPath Eur Clin Chem, 1941–2006
- Antibodies to citrullinated peptides: a significant step forward in the early diagnosis of rheumatoid arthritis
- Patient hydration: a major source of laboratory uncertainty
- Determination of the hepatitis C virus subtype: comparison of sequencing and reverse hybridization assays
- Quantification of relative changes in specific mRNAs from frozen whole blood – methodological considerations and clinical implications
- HER-2 protein concentrations in breast cancer cells increase before immunohistochemical and fluorescence in situ hybridization analysis turn positive
- Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis
- Novel molecular defect in the platelet ADP receptor P2Y12 of a patient with haemorrhagic diathesis
- Retrospective study of monoclonal gammopathies detected in the clinical laboratory of a Spanish healthcare district: 14-year series
- Renal impairment compromises the use of total homocysteine and methylmalonic acid but not total vitamin B12 and holotranscobalamin in screening for vitamin B12 deficiency in the aged
- Diagnostic value of calculated testosterone indices in the assessment of polycystic ovary syndrome
- Amniotic fibronectin fragmentation and expression of its domains, sialyl and fucosyl glycotopes associated with pregnancy complicated by intrauterine infection
- Predicted influence of sample hematocrit on injected mass of internal standard in mass spectrometry assays utilizing simple protein precipitation for sample preparation
- Evaluation of cardiovascular risk factors and related clinical markers in healthy young Japanese adults
- Cardiac natriuretic peptides after myocardial infarction: relationship with infarct size, left ventricular function and remodelling assessed by 99mTc-sestamibi gated-single photon emission tomography
- Plasma homocysteine cutoff values for venous thrombosis
- Lipid transfer protein activities in subjects with impaired glucose tolerance
- Heat shock protein 70-1 gene expression in pediatric heart surgery using blood cardioplegia
- Biochemical reference intervals for sex hormones with a new AutoDelfia method in aged men
- The Italian External Quality Control Programme for cystic fibrosis molecular diagnosis: 4 years of activity
- Standardization of ischemia-modified albumin testing: adjustment for serum albumin
- Is simultaneous measurement of anti-thyroid peroxidase and anti-thyroglobulin antibodies clinically useful in patients with thyroid dysfunction?
- To the Editor: In reply to Nakano et al. Clin Chem Lab Med 2006;44(5):522–532
- To the Editor: Author reply; Nakano et al. Clin Chem Lab Med 2006;44(5):522–532
- Accreditation of medical laboratories in the European Union
- Prevalence-dependent decision limits for the early detection of type 2 diabetes mellitus in venous blood, venous plasma and capillary blood during glucose challenge
Articles in the same Issue
- Associations between folate, vitamin B12, homocysteine and pathologies related to aging: the need to consider complex nutrient-nutrient and gene-nutrient interactions and the functional and socio-economic determinants in population-based studies
- Hyperhomocysteinemia and cardiovascular risk in postmenopausal women: the role of folate supplementation
- Association of vitamin B12, folate and homocysteine with functional and pathological characteristics of the elderly in a mountainous village in Sicily
- Association of thyroid dysfunction with vitamin B12, folate and plasma homocysteine levels in the elderly: a population-based study in Sicily
- Desmond (Des) Kenny MSc MCB FICI FRCPath Eur Clin Chem, 1941–2006
- Antibodies to citrullinated peptides: a significant step forward in the early diagnosis of rheumatoid arthritis
- Patient hydration: a major source of laboratory uncertainty
- Determination of the hepatitis C virus subtype: comparison of sequencing and reverse hybridization assays
- Quantification of relative changes in specific mRNAs from frozen whole blood – methodological considerations and clinical implications
- HER-2 protein concentrations in breast cancer cells increase before immunohistochemical and fluorescence in situ hybridization analysis turn positive
- Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis
- Novel molecular defect in the platelet ADP receptor P2Y12 of a patient with haemorrhagic diathesis
- Retrospective study of monoclonal gammopathies detected in the clinical laboratory of a Spanish healthcare district: 14-year series
- Renal impairment compromises the use of total homocysteine and methylmalonic acid but not total vitamin B12 and holotranscobalamin in screening for vitamin B12 deficiency in the aged
- Diagnostic value of calculated testosterone indices in the assessment of polycystic ovary syndrome
- Amniotic fibronectin fragmentation and expression of its domains, sialyl and fucosyl glycotopes associated with pregnancy complicated by intrauterine infection
- Predicted influence of sample hematocrit on injected mass of internal standard in mass spectrometry assays utilizing simple protein precipitation for sample preparation
- Evaluation of cardiovascular risk factors and related clinical markers in healthy young Japanese adults
- Cardiac natriuretic peptides after myocardial infarction: relationship with infarct size, left ventricular function and remodelling assessed by 99mTc-sestamibi gated-single photon emission tomography
- Plasma homocysteine cutoff values for venous thrombosis
- Lipid transfer protein activities in subjects with impaired glucose tolerance
- Heat shock protein 70-1 gene expression in pediatric heart surgery using blood cardioplegia
- Biochemical reference intervals for sex hormones with a new AutoDelfia method in aged men
- The Italian External Quality Control Programme for cystic fibrosis molecular diagnosis: 4 years of activity
- Standardization of ischemia-modified albumin testing: adjustment for serum albumin
- Is simultaneous measurement of anti-thyroid peroxidase and anti-thyroglobulin antibodies clinically useful in patients with thyroid dysfunction?
- To the Editor: In reply to Nakano et al. Clin Chem Lab Med 2006;44(5):522–532
- To the Editor: Author reply; Nakano et al. Clin Chem Lab Med 2006;44(5):522–532
- Accreditation of medical laboratories in the European Union
- Prevalence-dependent decision limits for the early detection of type 2 diabetes mellitus in venous blood, venous plasma and capillary blood during glucose challenge
