Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations
- 2 September 2016
- journal article
- research article
- Published by Archives of Pathology and Laboratory Medicine in Archives of Pathology & Laboratory Medicine
- Vol. 140 (12), 1331-1337
- https://doi.org/10.5858/arpa.2016-0157-ra
Abstract
Context.—In the burgeoning era of molecular genomics, immunoperoxidase (IPOX) testing grows increasingly relevant as an efficient and effective molecular screening tool. Patients with lung carcinoma may especially benefit from the use of IPOX because most lung carcinomas are inoperable at diagnosis and only diagnosed by small tissue biopsy or fine-needle sampling. When such small specimens are at times inadequate for molecular testing, positive IPOX results still provide actionable information. Objective.—To describe the benefits and pitfalls of IPOX in the detection of biomarkers in lung carcinoma cytology specimens and small biopsies by summarizing the currently available commercial antibodies, preanalytic variables, and analytic considerations. Data Sources.—PubMed. Conclusions.—Commercial antibodies exist for IPOX detection of aberrant protein expression due to EGFR L858R mutation, EGFR E746_A750 deletion, ALK rearrangement, ROS1 rearrangement, and BRAF V600E mutation, as well as PD-L1 expression in tumor cells. Automated IPOX protocols for ALK and PD-L1 detection were recently approved by the Food and Drug Administration as companion diagnostics for targeted therapies, but consistent interpretive criteria remain to be elucidated, and such protocols do not yet exist for other biomarkers. The inclusion of cytology specimens in clinical trials would expand patients' access to testing and treatment, yet there is a scarcity of clinical trial data regarding the application of IPOX to cytology, which can be attributed to trial designers' lack of familiarity with the advantages and limitations of cytology. The content of this review may be used to inform clinical trial design and advance IPOX validation studies.This publication has 61 references indexed in Scilit:
- Ascertaining an Appropriate Diagnostic Algorithm Using EGFR Mutation-Specific Antibodies to Detect EGFR Status in Non-Small-Cell Lung CancerPLOS ONE, 2013
- Molecular Characterization by Immunocytochemistry of Lung Adenocarcinoma on Cytology SpecimensActa Cytologica, 2012
- Chemical and physical basics of routine formaldehyde fixationJournal of Oral and Maxillofacial Pathology, 2012
- Suitability of Thoracic Cytology for New Therapeutic Paradigms in Non-small Cell Lung Carcinoma: High Accuracy of Tumor Subtyping and Feasibility of EGFR and KRAS Molecular TestingJournal of Thoracic Oncology, 2011
- Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancerJournal of Translational Medicine, 2010
- Novel Epidermal Growth Factor Receptor Mutation-Specific Antibodies for Non-small Cell Lung Cancer: Immunohistochemistry as a Possible Screening Method for Epidermal Growth Factor Receptor MutationsJournal of Thoracic Oncology, 2010
- Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung CancerNew England Journal of Medicine, 2010
- Assessment of EGFR Mutation Status in Lung Adenocarcinoma by Immunohistochemistry Using Antibodies Specific to the Two Major Forms of Mutant EGFRThe Journal of Molecular Diagnostics, 2010
- A Novel, Highly Sensitive Antibody Allows for the Routine Detection ofALK-Rearranged Lung Adenocarcinomas by Standard ImmunohistochemistryClinical Cancer Research, 2010
- Gefitinib or Carboplatin–Paclitaxel in Pulmonary AdenocarcinomaNew England Journal of Medicine, 2009