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ALK rearrangement in a large series of consecutive non-small cell lung cancers: comparison between a new immunohistochemical approach and fluorescence in situ hybridization for the screening of patients eligible for crizotinib treatment.
Arch Pathol Lab Med 2014; 138(11):1449-58AP

Abstract

CONTEXT

Echinoderm microtubule associated proteinlike 4-anaplastic lymphoma receptor tyrosine kinase (EML4-ALK) translocation has been described in a subset of patients with non-small cell lung cancer (NSCLC) and has been shown to have oncogenic activity. Fluorescence in situ hybridization (FISH) is used to detect ALK-positive NSCLC, but it is expensive, time-consuming, and difficult for routine application.

OBJECTIVE

To evaluate the potential role of immunohistochemistry (IHC) as a screening tool to identify candidate cases for FISH analysis and for ALK inhibitor therapy in NSCLC.

DESIGN

We performed FISH and IHC for ALK and mutational analysis for epidermal growth factor receptor (EGFR) and KRAS in 523 NSCLC specimens. We conducted IHC analysis with the monoclonal antibody D5F3 (Ventana Medical Systems, Tucson, Arizona) and a highly sensitive detection system. We also performed a MassARRAY-based analysis (Sequenom, San Diego, California) in a small subset of 11 samples to detect EML4-ALK rearrangement.

RESULTS

Of the 523 NSCLC specimens, 20 (3.8%) were positive for ALK rearrangement by FISH analysis. EGFR and KRAS mutations were identified in 70 (13.4%) and 124 (23.7%) of the 523 tumor samples, respectively. ALK rearrangement and EGFR and KRAS mutations were mutually exclusive. Of 523 tumor samples analyzed, 18 (3.4%) were ALK(+) by IHC, 18 samples (3.4%) had concordant IHC and FISH results, and 2 ALK(+) cases (0.3%) by FISH failed to show ALK protein expression. In the 2 discrepant cases, we did not detect any mass peaks for the EML4-ALK variants by MassARRAY.

CONCLUSIONS

Our results show that IHC may be a useful technique for selecting NSCLC cases to undergo ALK FISH analysis.

Authors+Show Affiliations

From the Units of Pathological Anatomy (Drs Alì, Proietti, Lupi, and Sensi and Ms Pelliccioni), Pneumology (Dr Chella), Endoscopic Section of Pneumology (Dr Ribechini), and Thoracic Surgery (Drs Melfi and Lucchi), Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; the Units of Pathological Anatomy (Ms Niccoli and Drs Giannini, Borrelli, and Fontanini) and Thoracic Surgery (Dr Mussi), Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy; Diatech Pharmacogenetics, Jesi, Italy (Dr Menghi); and the Department of Oncology, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy (Dr Cappuzzo).No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Evaluation Studies
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24885803

Citation

Alì, Greta, et al. "ALK Rearrangement in a Large Series of Consecutive Non-small Cell Lung Cancers: Comparison Between a New Immunohistochemical Approach and Fluorescence in Situ Hybridization for the Screening of Patients Eligible for Crizotinib Treatment." Archives of Pathology & Laboratory Medicine, vol. 138, no. 11, 2014, pp. 1449-58.
Alì G, Proietti A, Pelliccioni S, et al. ALK rearrangement in a large series of consecutive non-small cell lung cancers: comparison between a new immunohistochemical approach and fluorescence in situ hybridization for the screening of patients eligible for crizotinib treatment. Arch Pathol Lab Med. 2014;138(11):1449-58.
Alì, G., Proietti, A., Pelliccioni, S., Niccoli, C., Lupi, C., Sensi, E., ... Fontanini, G. (2014). ALK rearrangement in a large series of consecutive non-small cell lung cancers: comparison between a new immunohistochemical approach and fluorescence in situ hybridization for the screening of patients eligible for crizotinib treatment. Archives of Pathology & Laboratory Medicine, 138(11), pp. 1449-58. doi:10.5858/arpa.2013-0388-OA.
Alì G, et al. ALK Rearrangement in a Large Series of Consecutive Non-small Cell Lung Cancers: Comparison Between a New Immunohistochemical Approach and Fluorescence in Situ Hybridization for the Screening of Patients Eligible for Crizotinib Treatment. Arch Pathol Lab Med. 2014;138(11):1449-58. PubMed PMID: 24885803.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ALK rearrangement in a large series of consecutive non-small cell lung cancers: comparison between a new immunohistochemical approach and fluorescence in situ hybridization for the screening of patients eligible for crizotinib treatment. AU - Alì,Greta, AU - Proietti,Agnese, AU - Pelliccioni,Serena, AU - Niccoli,Cristina, AU - Lupi,Cristiana, AU - Sensi,Elisa, AU - Giannini,Riccardo, AU - Borrelli,Nicla, AU - Menghi,Maura, AU - Chella,Antonio, AU - Ribechini,Alessandro, AU - Cappuzzo,Federico, AU - Melfi,Franca, AU - Lucchi,Marco, AU - Mussi,Alfredo, AU - Fontanini,Gabriella, Y1 - 2014/06/02/ PY - 2014/6/3/entrez PY - 2014/6/3/pubmed PY - 2015/2/14/medline SP - 1449 EP - 58 JF - Archives of pathology & laboratory medicine JO - Arch. Pathol. Lab. Med. VL - 138 IS - 11 N2 - CONTEXT: Echinoderm microtubule associated proteinlike 4-anaplastic lymphoma receptor tyrosine kinase (EML4-ALK) translocation has been described in a subset of patients with non-small cell lung cancer (NSCLC) and has been shown to have oncogenic activity. Fluorescence in situ hybridization (FISH) is used to detect ALK-positive NSCLC, but it is expensive, time-consuming, and difficult for routine application. OBJECTIVE: To evaluate the potential role of immunohistochemistry (IHC) as a screening tool to identify candidate cases for FISH analysis and for ALK inhibitor therapy in NSCLC. DESIGN: We performed FISH and IHC for ALK and mutational analysis for epidermal growth factor receptor (EGFR) and KRAS in 523 NSCLC specimens. We conducted IHC analysis with the monoclonal antibody D5F3 (Ventana Medical Systems, Tucson, Arizona) and a highly sensitive detection system. We also performed a MassARRAY-based analysis (Sequenom, San Diego, California) in a small subset of 11 samples to detect EML4-ALK rearrangement. RESULTS: Of the 523 NSCLC specimens, 20 (3.8%) were positive for ALK rearrangement by FISH analysis. EGFR and KRAS mutations were identified in 70 (13.4%) and 124 (23.7%) of the 523 tumor samples, respectively. ALK rearrangement and EGFR and KRAS mutations were mutually exclusive. Of 523 tumor samples analyzed, 18 (3.4%) were ALK(+) by IHC, 18 samples (3.4%) had concordant IHC and FISH results, and 2 ALK(+) cases (0.3%) by FISH failed to show ALK protein expression. In the 2 discrepant cases, we did not detect any mass peaks for the EML4-ALK variants by MassARRAY. CONCLUSIONS: Our results show that IHC may be a useful technique for selecting NSCLC cases to undergo ALK FISH analysis. SN - 1543-2165 UR - https://www.unboundmedicine.com/medline/citation/24885803/ALK_rearrangement_in_a_large_series_of_consecutive_non_small_cell_lung_cancers:_comparison_between_a_new_immunohistochemical_approach_and_fluorescence_in_situ_hybridization_for_the_screening_of_patients_eligible_for_crizotinib_treatment_ L2 - http://www.archivesofpathology.org/doi/10.5858/arpa.2013-0388-OA?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -