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Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

TitleChromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2010
AuthorsSimone, G., Mangia A., Malfettone A., Rubini V., Siciliano M., Di Benedetto A., Terrenato I., Novelli Flavia, and Mottolese M.
JournalJournal of Experimental and Clinical Cancer Research
Volume29
ISSN17569966
Keywords80 and over, adenocarcinoma, adult, aged, aneuploidy, article, aspiration biopsy, aspiration cytology, Biopsy, biotin, Carcinoma, chemistry, Chromogenic Compounds, chromogenic in situ hybridization, chromogenic substrate, chromosome 7, Chromosomes, clinical article, colorectal cancer, Colorectal Neoplasms, colorectal tumor, comparative study, computer assisted tomography, controlled study, copy number variation, diagnostic agent, digoxigenin, EGFR protein, Epidermal Growth Factor, epidermal growth factor receptor, evaluation, Feasibility studies, feasibility study, Female, Fine-Needle, fluorescence, fluorescence in situ hybridization, gene amplification, gene dosage, gene expression regulation, gene overexpression, genetics, human, human tissue, Humans, immunohistochemistry, In Situ Hybridization, Italy, large cell carcinoma, lung metastasis, Lung Neoplasms, lung nodule, lung non small cell cancer, lung tumor, male, metastasis, methodology, Middle Aged, needle biopsy, Neoplastic, Non-Small-Cell Lung, Pair 7, Pathology, predictive validity, predictive value, Predictive Value of Tests, priority journal, Receptor, reproducibility, Reproducibility of Results, Retrospective Studies, retrospective study, Sensitivity and Specificity, squamous cell carcinoma
Abstract

Background. Several studies demonstrated that epidermal growth factor receptor (EGFR) gene copy number (GCN) correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC) and to anti-EGFR monoclonal antibodies (MoAbs) in metastatic colorectal cancer (CRC). In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic in situ hybridization (CISH) is an alternative technique to fluorescence in situ hybridization (FISH), but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC) of lung nodules has not yet been established. Methods. We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas) and 13 lung metastases from CRC. Results. Of the 33 FNAC analyzed by CISH, 27 (82%) presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30%) showed a low polysomy, 15 (45%) a high polysomy and 2 (6%) NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p < 0.0001). Two cases were amplified with both assays, whereas 1 case of NSCLC was amplified by FISH only. CISH sensitivity was 67%, the specificity and positive predictive value (PPV) was 100%, and the negative predictive value (NPV) was 97%. Conclusions. Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung. © 2010 Simone et al; licensee BioMed Central Ltd.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-77956509378&doi=10.1186%2f1756-9966-29-125&partnerID=40&md5=dbb67ea6d25ca473b0dfa28be8f550d3
DOI10.1186/1756-9966-29-125
Citation KeySimone2010