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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.

ABSTRACT: OBJECTIVE: Epidermal growth factor receptor (EGFR) and K-ras mutations guide treatment selection in non-small 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.

SUBMITTER: Lozano MD

PROVIDER: S-EPMC3228207 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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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.

Lozano Maria D MD Zulueta Javier J JJ Echeveste Jose I JI Gúrpide Alfonso A Seijo Luis M LM Martín-Algarra Salvador S Del Barrio Anabel A Pio Ruben R Idoate Miguel Angel MA Labiano Tania T Perez-Gracia Jose Luis JL

The oncologist 20110514 6

<h4>Objective</h4>Epidermal growth factor receptor (EGFR) and K-ras mutations guide treatment selection in non-small 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.<h4>Methods</h4>DNA was extracted from 150 consecutive samples, including 120 Papanicolau smears (80%), 10 cell blocks (7%), nine fresh samples (6%), six ThinPre ...[more]

PMID: 21572125

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Project description:BackgroundMalaria parasitemia is commonly used as a measurement of the amount of parasites in the patient's blood and a crucial indicator for the degree of infection. Manual evaluation of Giemsa-stained thin blood smears under the microscope is onerous, time consuming and subject to human error. Although automatic assessments can overcome some of these problems the available methods are currently limited by their inability to evaluate cases that deviate from a chosen "standard" model.ResultsIn this study reliable parasitemia counts were achieved even for sub-standard smear and image quality. The outcome was assessed through comparisons with manual evaluations of more than 200 sample smears and related to the complexity of cell overlaps. On average an estimation error of less than 1% with respect to the average of manually obtained parasitemia counts was achieved. In particular the results from the proposed approach are generally within one standard deviation of the counts provided by a comparison group of malariologists yielding a correlation of 0.97. Variations occur mainly for blurred out-of-focus imagery exhibiting larger degrees of cell overlaps in clusters of erythrocytes. The assessment was also carried out in terms of precision and recall and combined in the F-measure providing results generally in the range of 92% to 97% for a variety of smears. In this context the observed trade-off relation between precision and recall guaranteed stable results. Finally, relating the F-measure with the degree of cell overlaps, showed that up to 50% total cell overlap can be tolerated if the smear image is well-focused and the smear itself adequately stained.ConclusionThe automatic analysis has proven to be comparable with manual evaluations in terms of accuracy. Moreover, the test results have shown that the proposed comparison-based approach, by exploiting the interrelation between different images and color channels, has successfully overcome most of the inherent limitations possibly occurring during the sample preparation and image acquisition phase. Eventually, this can be seen as an opportunity for developing low-cost solutions for mass screening.

Dataset Information

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.

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.

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