Evaluation of epidermal growth factor receptor mutations based on mutation specific immunohistochemistry in non-small cell lung cancer: A preliminary study

Abstract

Background & objectives:Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC).Methods:Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed.Results:Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon20 variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases.Interpretation & conclusions:In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests.

Use of Exfoliative Specimens and Fine-Needle Aspiration Smears for Mutation Testing in Lung Adenocarcinoma

“…The clinical implications of the exon 20 polymorphism need to be further investigated. We found 19.5% EGFR mutations, with EGFR exon 19 deletions and exon 21 mutations being the most prevalent, similar to previously published data [30] . The lower prevalence of EGFR mutations in cytology samples may possibly be attributed to a selection bias; we used only those cases where tumor cellularity was good and where enough diagnostic FNA smears were available in our archives to mitigate medicolegal issues.…”

Adenocarcinoma predominant pattern subtyping and nuclear grading in cytology: Is there a role in prognostication of advanced pulmonary adenocarcinomas?

“…Among ADs alone, one previous study showed that cytological features correlate with prognosis, while others found that pattern grading on small biopsies predicts response to chemotherapy . In addition, knowledge of the varied patterns of lung ADs and its recognition will aid in triage of material for molecular analysis …”

“…[10][11][12][13] In addition, knowledge of the varied patterns of lung ADs and its recognition will aid in triage of material for molecular analysis. [14][15][16] We aimed to predict architectural patterns and analyse nuclear grades of lung ADs on cytology, correlate their concordance with predominant pattern on paired small biopsies, and to assess outcome.…”

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer

“…In Caucasian populations 10% of patients harbor these mutations, while in East Asian patients the frequency has been reported to be as high as 60% [14,15] . In the Indian population, where there is genetic diversity, a frequency of 23-50% has been reported ( table 2 ) [16][17][18][19][20][21][22][23] . The techniques of mutation testing as well as the type of referrals have varied in these studies.…”