[Molecular protocol for HER2/neu analysis in breast carcinoma]
| Autor: | Montse Verdú, Artufel, Anna Colomer, Valero, Ruth Román, Lladó, Nadina Erill, Sagalés, Miquel Calvo, Llorca, Abelardo Moreno, Carazo, Carlos Cordón, Cardó, Xavier Puig, Torrus |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Aged 80 and over Male Receptor ErbB-2 Carcinoma Ductal Breast Gene Amplification Antibodies Monoclonal Breast Neoplasms Genes erbB-2 Middle Aged Adenocarcinoma Mucinous Proto-Oncogene Mas Sensitivity and Specificity Breast Neoplasms Male Neoplasm Proteins Immunoenzyme Techniques Carcinoma Lobular Humans False Positive Reactions Female Prospective Studies Algorithms In Situ Hybridization Fluorescence Aged |
| Zdroj: | Clinicaltranslational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 7(11) |
| ISSN: | 1699-048X |
| Popis: | The HER2/neu proto-oncogene is frequently over-expressed in breast cancer and serves as a biological target for trastuzumab therapy. However, there is no consensus regarding the technical aspects to be used to define HER2/neu status in clinical practice.The present study was conducted to address this critical issue by prospectively analysing a large cohort of breast cancer patients (n = 222) and using a variety of methods. To define HER2/neu expression, detection of its encoded protein (p185) was performed by comparative immunohistochemical (IHC) analysis using two mouse monoclonal antibodies (mAb CB11 and mAb TAB250). To assess HER2/neu gene amplification, fluorescent in situ hybridisation (FISH) assays with gene-specific probes were conducted. All procedures were applied to de-paraffinised tissue sections of breast tumour samples.Results showed that mAb CB11 had increased sensitivity and specificity (62.5% and 93.4%, respectively) compared to mAb TAB250 (40% and 76.4%, respectively) in defining HER2/neu amplification. We conclude that HER2/neu measurement by IHC using mAb CB11 is an appropriate strategy which provides a high negative predictive value (95.5%) for HER2/neu amplification in cases with low or undetectable p185 expression. Conversely, mAb CB11 has a high positive predictive value (96.2%) for HER2/neu amplification in cases with p185 overexpression. However, cases with moderate p185 expression need to be considered as inconclusive. In such cases, it is necessary to use FISH measurement to evaluate HER2/neu amplification. It is also advisable to conduct FISH if there is discordance between p185 expression and the histopathology classification of the lesion, or molecular profile of the tumour. Finally, even though the false positive rate of IHC assay is5%, the toxicity and cost of trastuzumab therapy suggest that FISH be used systematically prior to implementation of treatment.We suggest the use of a molecular protocol for HER2/neu analysis in this type of tumor. |
| Databáze: | OpenAIRE |
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