Use of mutation specific antibodies to detect EGFR status in small biopsy and cytology specimens of lung adenocarcinoma

Hasanovic, Adnan; Ang, Daphne; Moreira, André L.; Zakowski, Maureen F.

doi:10.1016/j.lungcan.2012.04.004

Cited by 47 publications

(42 citation statements)

References 37 publications

(58 reference statements)

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“…It can thus improve patients' access to the molecular characterization of tumors by acting as an alternative or adjunct method to molecular techniques. 8,18 Furthermore, most laboratories can run IPOX tests, most pathologists are familiar with the interpretation of these tests, and IPOX results can be available within 24 hours in most laboratories. A positive IPOX result has the potential to guide patient management while avoiding rebiopsy, which is an important consideration for patients who may not be able to tolerate additional biopsy procedures.…”

Section: Cytology Specimensmentioning

confidence: 99%

“…The sensitivity of the antibodies has been reported to be 76%-90% for L858R and 80%-90% for E746_A750del, both with specificity and positivity predictive values ranging from 99% to 100% in both histologic sections and cytologic preparations. 7,18 The antibody that detects E746_A750del has been shown in some studies to have lower sensitivity; however, this is mostly due to the studies' inclusion of non-E746_A750 exon 19 deletions. 33,34 Up to 35% of exon 19 deletions are not E746_A750del.…”

Section: Egfr Antibodiesmentioning

confidence: 99%

“…Hasanovic et al 18 showed that a binary scoring system based on the evaluation of the intensity of membranous and cytoplasmic staining patterns correlates with mutation status; the system is verified by standard molecular tests and validated in cytology material. Briefly, absence of tumor cell staining (0) and faint cytoplasmic or incomplete membranous staining (1þ) are considered negative.…”

Section: Egfr Antibodiesmentioning

confidence: 99%

“…When the decalcification of a bone core biopsy renders the biopsy unsuitable for molecular testing, a positive reaction by IPOX provides useful information. 18 Because IPOX results can be reported in 24 hours, providing clinicians with actionable data while they await the more comprehensive results of next-generation sequencing, these mutation-specific EGFR antibodies are now routinely being used to screen for EGFR mutations. Given that the commercially available mutant EGFR antibodies have a sensitivity of approximately 80%, a lack of reactivity does not exclude the possible existence of other sensitizing mutations in the EGFR gene.…”

Section: Egfr Antibodiesmentioning

confidence: 99%

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Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations

Zhou

Moreira²

2016

Archives of Pathology &Amp; Laboratory Medicine

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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.

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Section: Cytology Specimensmentioning

confidence: 99%

Section: Egfr Antibodiesmentioning

confidence: 99%

Section: Egfr Antibodiesmentioning

confidence: 99%

Section: Egfr Antibodiesmentioning

confidence: 99%

See 2 more Smart Citations

Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations

Zhou

Moreira²

2016

Archives of Pathology &Amp; Laboratory Medicine

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“…[22][23][24][25][26][27][28][29][30][31][32]44 Mutation-specific EGFR antibodies do not yet account for all potentially actionable mutations, although they may have a possible role in initial screening. [45][46][47] The EGFR mutation/EGFR TKI story has generated a great deal of excitement and hope among lung cancer patients, their families and friends, oncologists, pathologists, and the lay public. However, EGFR TKI therapy, as exciting as it is and as important as it is to a subset of patients, is far from a cure-all for lung cancer.…”

mentioning

confidence: 99%

Verifying the Role of Surgical Pathologists in the Precision Medicine of Lung Cancer

Cagle

Olsen

2012

Archives of Pathology &Amp; Laboratory Medicine

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Immunocytochemistry for predictive biomarker testing in lung cancer cytology

Jain

Nambirajan

Borczuk

et al. 2019

Cancer Cytopathology

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114

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With an escalating number of predictive biomarkers emerging in non-small cell lung carcinoma (NSCLC), immunohistochemistry (IHC) is being used as a rapid and cost-effective tool for the screening and detection of many of these markers.In particular, robust IHC assays performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue are widely used as surrogate markers for ALK and ROS1 rearrangements and for detecting programmed death ligand 1 (PD-L1) expression in patients with advanced NSCLC; in addition, they have become essential for treatment decisions. Cytology samples represent the only source of tumor in a significant proportion of patients with inoperable NSCLC, and there is increasing demand for predictive biomarker testing on them. However, the wide variation in the types of cytology samples and their preparatory methods, the use of alcohol-based fixatives that interfere with immunochemistry results, the difficulty in procurement of cytology-specific controls, and the uncertainty regarding test validity have resulted in underutilization of cytology material for predictive immunocytochemistry (ICC), and most cytopathologists limit such testing to FFPE cell blocks (CBs). The purpose of this review is to: 1) analyze various preanalytical, analytical, and postanalytical factors influencing ICC results; 2) discuss measures for validation of ICC protocols; and 3) summarize published data on predictive ICC for ALK, ROS1, EGFR gene alterations and PD-L1 expression on lung cancer cytology. Based on our experience and from a review of the literature, we conclude that cytology specimens are in principal suitable for predictive ICC, but proper optimization and rigorous quality control for high-quality staining are essential, particularly for non-CB preparations.

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Use of mutation specific antibodies to detect EGFR status in small biopsy and cytology specimens of lung adenocarcinoma

Cited by 47 publications

References 37 publications

Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations

Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations

Verifying the Role of Surgical Pathologists in the Precision Medicine of Lung Cancer

Immunocytochemistry for predictive biomarker testing in lung cancer cytology

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