Detection of EGFR Mutations in Archived Cytologic Specimens of Non-Small Cell Lung Cancer Using High-Resolution Melting Analysis

Nomoto, Kiyoaki; Tsuta, Koji; Takano, Toshimi; Fukui, Tomoya; Yokozawa, Karin; Sanada, Hiromi; Yoshida, Teruhiko; Maeshima, Akiko Miyagi; Shibata, Tatsuhiro; Furuta, Koh; Ohe, Yuichiro; Matsuno, Yoshihiro

doi:10.1309/n5pq-ngw2-qkmx-09x7

Cited by 68 publications

(103 citation statements)

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“…Boldrini et al [28] reported their retrospective results from a small series of 23 cytological samples. Nomoto et al [29] and Smith et al [30] analyzed the feasibility of a high-resolution melting analysis to perform EGFR mutational analysis in small specimens, including cytological samples. Fukui et al [31] reported their results with small diagnostic samples and biopsies from 92 patients.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Epidermal Growth Factor Receptor and K-Ras Mutation Status in Cytological Stained Smears of Non-Small Cell Lung Cancer Patients: Correlation with Clinical Outcomes

et al. 2011

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Objective. Epidermal growth factor receptor (EGFR) and K-ras mutations guide treatment selection in nonsmall cell lung cancer (NSCLC) patients. Although mutation status is routinely assessed in biopsies, cytological specimens are frequently the only samples available. We determined EGFR and K-ras mutations in cytological samples.Methods. DNA was extracted from 150 consecutive samples, including 120 Papanicolau smears (80%), 10 cell blocks (7%), nine fresh samples (6%), six ThinPrep tests (4%), and five body cavity fluids (3.3%). Papanicolau smears were analyzed when they had >50% malignant cells. Polymerase chain reaction and direct sequencing of exons 18 -21 of EGFR and exon 2 of K-ras were performed. EGFR mutations were simultaneously determined in biopsies and cytological samples from 20 patients. Activity of EGFR tyrosine kinase inhibitors (TKIs) was assessed.Results. The cytological diagnosis was adenocarcinoma in 110 samples (73%) and nonadenocarcinoma in 40 (27%) samples. EGFR mutations were identified in 26 samples (17%) and K-ras mutations were identified in 18 (12%) samples. EGFR and K-ras mutations were mutually exclusive. In EGFR-mutated cases, DNA was obtained from stained smears in 24 cases (92%), pleural fluid in one case (4%), and cell block in one case (4%). The response rate to EGFR TKIs in patients harboring mutations was 75%. The mutation status was identical in patients who had both biopsies and cytological samples analyzed.Conclusion. Assessment of EGFR and K-ras mutations in cytological samples is feasible and comparable with biopsy results, making individualized treatment selection possible for NSCLC patients from whom tumor biopsies are not available. The Oncologist 2011;16: 877-885

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Section: Discussionmentioning

confidence: 99%

Assessment of Epidermal Growth Factor Receptor and K-Ras Mutation Status in Cytological Stained Smears of Non-Small Cell Lung Cancer Patients: Correlation with Clinical Outcomes

et al. 2011

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“…In a previous study 29 on colorectal cancer, we demonstrated the high sensitivity of HRM analysis, which allowed identifying at least 5% of mutated alleles in a background of wild-type DNA. Even though HRM analysis has been widely applied for the screening of somatic variants in biopsies of solid cancers, only a few previous applications of HRM analysis have been reported in the screening of cytological material, as fixed fresh cells 36 or scraped cells from archival slides 37 obtained from needle aspiration.…”

Section: Discussionmentioning

confidence: 99%

A High-Resolution Melting Protocol for Rapid and Accurate Differential Diagnosis of Thyroid Nodules

Mancini

Pinzani

Pupilli

et al. 2012

The Journal of Molecular Diagnostics

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Thyroid cancer is the most common malignancy of the endocrine system, accounting for approximately 1% of all malignancies in Western countries. 1 The incidence of thyroid cancer has increased 2.6-fold in the last 30 years. This change is attributed not only to an increment in papillary thyroid carcinoma, 2 but also to more wisely conducted medical surveillance and improvements in diagnostic tools. 3 The large majority of thyroid nodules, as discovered with the use of new diagnostic imaging techniques, are asymptomatic and benign. In this context, diagnostic studies are becoming essential to identify the small fraction of thyroid nodules that harbor malignant disease and to predict when surgery is indicated. Fine-needle aspiration biopsy (FNAB) has emerged over the past 30 years as an accurate and cost-effective procedure for the preoperative screening of thyroid nodules, representing the gold standard for differential diagnosis of benign and malignant nodules. 4 Under recent guidelines, 5,6 cytological smears are classified in five categories for the diagnostic report: Thy 1, nondiagnostic; Thy 2, benign or negative for malignant cells; Thy 3, all follicular lesions (including atypia/ follicular lesion of undetermined significance and follicular neoplasm or suspicious for follicular neoplasm); Thy 4, suspicious; and Thy 5, diagnostic for malignancy.Although the overall accuracy of FNAB is considered excellent, approximately 30% of cytological aspirates do not allow definitive diagnosis of malignancy, because of intrinsic and unavoidable characteristics of samples. 7 The major limitations of FNAB procedures are linked to inadequate and indeterminate specimens and, in that sense, are also linked respectively to the nondiagnostic or follicular lesions categories. 8,9 Thus, a clinical need emerges for the characterization of aspirates with suspicious features but with unsatisfactory cellularity, to allow accurate distinction of benign from malignant forms of follicular lesions.Several somatic mutations have been identified in thyroid cancer, stimulating the search for genetic alterations in FNAB that could increase the diagnostic accuracy of traditional cytology. Numerous studies have demonstrated that identification of specific mutations in cytological specimens can assist in the diagnosis by FNAB and in the clinical decision to excise the nodule and to intensify the follow-up. 10 -16 In most cases, genetic alterations are represented by activating mutations of oncogenes that are mutually exclusive and linked to distinct histological subtypes, with a demonstrated pathogenic role in thyroid cell transformation as effectors of the RAS/RAF/ MAPK signaling cascade.The presence of BRAF mutations, a frequent alteration in papillary carcinoma (PTC), evolves into an unregulated activation of the intracellular MAPK pathway that can promote tumorigenesis and tumor progression. The main mutation of BRAF, identified exclusively in PTC, affects

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“…However, confirmation of mutations via direct sequencing is still necessary. 27, 76,77 Though not of any current clinical use, an assay that provides a rapid assessment of EGFR mutation status in as little as 30 min using a 'smart amplification process' has been described. These may one day provide greatly improved turnaround times for this analysis.…”

Section: Egfr Mutationsmentioning

confidence: 99%

Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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The majority of lung adenocarcinoma patients with epidermal growth factor receptor-(EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

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Detection of EGFR Mutations in Archived Cytologic Specimens of Non-Small Cell Lung Cancer Using High-Resolution Melting Analysis

Cited by 68 publications

References 0 publications

Assessment of Epidermal Growth Factor Receptor and K-Ras Mutation Status in Cytological Stained Smears of Non-Small Cell Lung Cancer Patients: Correlation with Clinical Outcomes

Assessment of Epidermal Growth Factor Receptor and K-Ras Mutation Status in Cytological Stained Smears of Non-Small Cell Lung Cancer Patients: Correlation with Clinical Outcomes

A High-Resolution Melting Protocol for Rapid and Accurate Differential Diagnosis of Thyroid Nodules

Molecular pathology of lung cancer: key to personalized medicine

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