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Lung Cancer. 2015 Aug;89(2):104-9. doi: 10.1016/j.lungcan.2015.05.012. Epub 2015 May 21.

Screening for ALK in non-small cell lung carcinomas: 5A4 and D5F3 antibodies perform equally well, but combined use with FISH is recommended.

Author information

1
Institute of Pathology, University Hospital Basel, Schoenbeinstrasse 40, 4031 Basel, Switzerland. Electronic address: spasenija.savicprince@usb.ch.
2
Institute of Pathology, Cantonal Hospital Lucerne, 6000 Luzern 16, Lucerne, Switzerland. Electronic address: Joachim.Diebold@luks.ch.
3
Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland. Electronic address: ak.zimmermann@gmx.de.
4
Institute of Pathology, Cantonal Hospital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland. Electronic address: Wolfram.Jochum@kssg.ch.
5
Institute of Pathology, University Hospital Basel, Schoenbeinstrasse 40, 4031 Basel, Switzerland. Electronic address: betty.baschiera@usb.ch.
6
Institute of Pathology, University Hospital Basel, Schoenbeinstrasse 40, 4031 Basel, Switzerland. Electronic address: susanne.grieshaber@usb.ch.
7
Institute of Pathology, University Hospital Basel, Schoenbeinstrasse 40, 4031 Basel, Switzerland. Electronic address: luigi.tornillo@unibas.ch.
8
Institute of Pathology, University Hospital Lausanne, Rue du Bugnon 25, 1011 Lausanne, Switzerland. Electronic address: Bettina.Bisig@chuv.ch.
9
Department of Pathology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address: k.kerr@abdn.ac.uk.
10
Institute of Pathology, University Hospital Basel, Schoenbeinstrasse 40, 4031 Basel, Switzerland. Electronic address: lukas.bubendorf@usb.ch.

Abstract

OBJECTIVES:

Immunohistochemistry (IHC) has become a promising method for pre-screening ALK-rearrangements in non-small cell lung carcinomas (NSCLC). Various ALK antibodies, detection systems and automated immunostainers are available. We therefore aimed to compare the performance of the monoclonal 5A4 (Novocastra, Leica) and D5F3 (Cell Signaling, Ventana) antibodies using two different immunostainers. Additionally we analyzed the accuracy of prospective ALK IHC-testing in routine diagnostics.

MATERIALS AND METHODS:

Seventy-two NSCLC with available ALK FISH results and enriched for FISH-positive carcinomas were retrospectively analyzed. IHC was performed on BenchMarkXT (Ventana) using 5A4 and D5F3, respectively, and additionally with 5A4 on Bond-MAX (Leica). Data from our routine diagnostics on prospective ALK-testing with parallel IHC, using 5A4, and FISH were available from 303 NSCLC.

RESULTS:

All three IHC protocols showed congruent results. Only 1/25 FISH-positive NSCLC (4%) was false negative by IHC. For all three IHC protocols the sensitivity, specificity, positive (PPV) and negative predictive values (NPV) compared to FISH were 96%, 100%, 100% and 97.8%, respectively. In the prospective cohort 3/32 FISH-positive (9.4%) and 2/271 FISH-negative (0.7%) NSCLC were false negative and false positive by IHC, respectively. In routine diagnostics the sensitivity, specificity, PPV and NPV of IHC compared to FISH were 90.6%, 99.3%, 93.5% and 98.9%, respectively.

CONCLUSIONS:

5A4 and D5F3 are equally well suited for detecting ALK-rearranged NSCLC. BenchMark and BOND-MAX immunostainers can be used for IHC with 5A4. True discrepancies between IHC and FISH results do exist and need to be addressed when implementing IHC in an ALK-testing algorithm.

KEYWORDS:

5A4; ALK; D5F3; FISH; Immunohistochemistry; Lung cancer

PMID:
26056079
DOI:
10.1016/j.lungcan.2015.05.012
[Indexed for MEDLINE]

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