EGFR Gene Alterations in a Norwegian Cohort of Lung Cancer Patients Selected for Surgery

Helland, Åslaug; Skaug, Hege Marian; Kleinberg, Lilach; Iversen, Marius Lund; Rud, Ane Kongsgaard; Fleischer, Thomas; Sagerup, Camilla M T; Solberg, Steinar; Jørgensen, Lars; Ariansen, Sarah; Brustugun, Odd Terje

doi:10.1097/jto.0b013e31820db209

Cited by 39 publications

(42 citation statements)

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“…These were investigations on resection specimens, an earlier one from Italy with a 4.5% occurrence [15], and a recent one from Norway (6.6% [16]). In another of our series on resection specimens, the frequency was lower as well at 7.0% (personal communication C. Dooms).…”

Section: Resultsmentioning

confidence: 99%

Performance of standard procedures in detection of EGFR mutations in daily practice in advanced NSCLC patients selected according to the ESMO guideline: a large Caucasian cohort study

et al. 2014

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BackgroundESMO consensus recommends EGFR mutation testing in never/former light smokers (<15 pack-years) or patients with non-squamous NSCLC. The aim of this work was to determine the frequency and clinical predictors of EGFR mutations, and the role of specimen sampling tests, in Caucasian standard practice setting.MethodsWe screened 297 patients according to this consensus. Mutational analysis of EGFR was performed using the Therascreen EGFR RGQ PCR mutation kit. Clinical and pathological correlative data were collected.ResultsAn EGFR activating mutation was found in 32 patients (11%), twelve exon 19 deletions, two exon 18 and eighteen exon 21 point mutations. Most were in females, but half were in smokers. Negative TTF-1 staining had a very strong negative predictive value (all except one patient had TTF-1 positive adenocarcinoma). Both biopsies as well as cytology specimens (mainly EBUS-TBNA) did well: 24 mutations in 213 biopsy samples (11.2%) and 8 in 84 cytology samples (9.5%), respectively. The Therascreen acted as a sensitive test in all types of samples: 7 activating mutations were found in samples rated to have <5% of tumour cells, and there were only 4 test failures in the whole series.ConclusionIn this Caucasian standard practice NSCLC cohort, tested according to the ESMO consensus, activating EGFR mutation occurred in 11% of the patients. Half of these were in former/current smokers. With our sampling technique and use of the Therascreen kit, EBUS-TBNA cell blocks performed as good as biopsies.

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Section: Resultsmentioning

confidence: 99%

Performance of standard procedures in detection of EGFR mutations in daily practice in advanced NSCLC patients selected according to the ESMO guideline: a large Caucasian cohort study

et al. 2014

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“…The prevalence of the EGFR-TKI-sensitive mutation was high in AD in an Asian population, but was low in Caucasians [50][51][52][53][54]. The full range of genetic factors involved in the susceptibility to lung cancer are still unclear, but some studies have suggested an association between family history and the risk of lung cancer, especially in the case of AD [55].…”

Section: Differences In Lung Cancer Among Ethnicitiesmentioning

confidence: 99%

A worldwide trend of increasing primary adenocarcinoma of the lung

Nakamura

Saji

2013

Surg Today

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The four major histological types of lung cancer are adenocarcinoma, squamous cell carcinoma (SQ), large cell carcinoma and small cell carcinoma. Over the past few decades, the incidence of lung adenocarcinoma has increased gradually in most countries as the most frequently occurring histological type, displacing SQ. Adenocarcinoma is the predominant type of lung cancer among lifelong non-smokers and among females. Especially in East Asian countries, the cause(s) of the increase in adenocarcinomas are not clear. Several genetic mutations specific to lung adenocarcinomas have been found, representing attractive targets for molecular therapy. Recently, the pathological classification of lung adenocarcinoma was revised by integrating the newer clinical and biological knowledge concerning this prevailing type. Additional epidemiological, pathological and genetic studies are required to better understand this type of lung cancer.

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“…Several other EGFR mutations have been reported, but their clinical significance is yet unknown. Mutation rate in adenocarcinomas in East Asian patients are 20-50% 9 and 5-15% in Western European patients depending on whether selected 9 or unselected [10][11][12][13] patients are tested.…”

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confidence: 99%

High specificity but low sensitivity of mutation-specific antibodies against EGFR mutations in non-small-cell lung cancer

et al. 2014

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Determination of epidermal growth factor receptor (EGFR) mutations has a pivotal impact on treatment of non-small-cell lung cancer (NSCLC). A standardized test has not yet been approved. So far, Sanger DNA sequencing has been widely used. Its rather low sensitivity has led to the development of more sensitive methods including real-time PCR (RT-PCR). Immunohistochemistry with mutation-specific antibodies might be a promising detection method. We evaluated 210 samples with NSCLC from an unselected Caucasian population. Extracted DNA was analyzed for EGFR mutations by RT-PCR (Therascreen EGFR PCR kit, Qiagen, UK; reference method). For immunohistochemistry, antibodies against exon19 deletions (clone 6B6), exon21 mutations (clone 43B2) from Cell Signaling Technology (Boston, USA) and EGFR variantIII (clone 218C9) from Dako (Copenhagen, DK) were applied. Protein expression was evaluated, and staining score (multipum of intensity (graded 0-3) and percentages (0-100%) of stained tumor cells) was calculated. Positivity was defined as staining score 40. Specificity of exon19 antibody was 98.8% (95% confidence interval ¼ 95.9-99.9%) and of exon21 antibody 97.8% (95% confidence interval ¼ 94.4-99.4%). Sensitivity of exon19 antibody was 63.2% (95% confidence interval ¼ 38.4-83.7%) and of exon21 antibody was 80.0% (95% confidence interval ¼ 44.4-97.5%). Seven exon19 and four exon21 mutations were false negatives (immunohistochemistry negative, RT-PCR positive). Two exon19 and three exon21 mutations were false positive (immunohistochemistry positive, RT-PCR negative). One false positive exon21 mutation had staining score 300. The EGFR variantIII antibody showed no correlation to EGFR mutation status determined by RT-PCR or to EGFR immunohistochemistry. High specificity of the mutation-specific antibodies was demonstrated. However, sensitivity was low, especially for exon19 deletions, and thus these antibodies cannot yet be used as screening method for EGFR mutations in NSCLC. Refinement of sensitivity for the mutation-specific antibodies is warranted to improve molecular diagnosis using EGFR immunohistochemistry.

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EGFR Gene Alterations in a Norwegian Cohort of Lung Cancer Patients Selected for Surgery

Abstract: The frequency of EGFR mutations is lower in our cohort than among Asian lung cancer patients and present in both men and women and smokers and never-smokers. However, the frequency is significantly higher among women and never-smokers and among patients with adenocarcinomas.

Cited by 39 publications

References 10 publications

Performance of standard procedures in detection of EGFR mutations in daily practice in advanced NSCLC patients selected according to the ESMO guideline: a large Caucasian cohort study

Performance of standard procedures in detection of EGFR mutations in daily practice in advanced NSCLC patients selected according to the ESMO guideline: a large Caucasian cohort study

A worldwide trend of increasing primary adenocarcinoma of the lung

High specificity but low sensitivity of mutation-specific antibodies against EGFR mutations in non-small-cell lung cancer

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