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. 2013 Nov 15;6(12):2800-12.
eCollection 2013.

EGFR mutation testing on cytological and histological samples in non-small cell lung cancer: a Polish, single institution study and systematic review of European incidence

Anna Szumera-Ciećkiewicz  1 , Włodzimierz T Olszewski, Andrzej Tysarowski, Dariusz M Kowalski, Maciej Głogowski, Maciej Krzakowski, Janusz A Siedlecki, Michał Wągrodzki, Monika Prochorec-Sobieszek
Affiliations

EGFR mutation testing on cytological and histological samples in non-small cell lung cancer: a Polish, single institution study and systematic review of European incidence

Anna Szumera-Ciećkiewicz et al. Int J Clin Exp Pathol. .

Abstract

The targeted treatment of advanced non-small-cell lung cancer (NSCLC) depends on confirmation of activating somatic EGFR mutation. The aim of the study was to evaluate the incidence of EGFR mutations in NSCLC detected in cytological and histological material and present literature review on European EGFR mutation incidence. 273 patients with confirmed NSCLC were entered into the study: 189 histological, paraffin-embedded materials, 12 fresh and 72 fixed cytological specimens. DNA was extracted from both types of material and the EGFR mutation in exons 18-21 was analyzed by direct sequencing. In addition the EGFR gene copy number in cases with sufficient histological material (110 patients) was evaluated by fluorescent in situ hybridization (FISH) technique. The percentage of EGFR somatic mutations was 10.62%. FISH positive results (amplification or high polysomy of EGFR gene) were identified in 33 patients (30.0%). The strongest clinicopathological correlation with the EGFR mutation was found for histological type (adenocarcinoma; p < 0.01), gender (females; p < 0.01) and FISH positive result (p < 0.05). This is the first, single institution study that estimates the EGFR mutation incidence in the Polish population. Cytological material recovered from fixed preparations and stained with hematoxylin and eosin showed DNA quality comparable to fresh tumor cells and histological samples.

Keywords: EGFR amplification; EGFR mutation; cytology; non-small-cell lung cancer.

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Figures

Figure 1
Figure 1
Images of the most frequent histological and molecular results [A: Adenocarcinoma, papillary subtype (HE, 400 x), B: Embolism of adenocarcinoma cells in the lymphatic vessel (TTF-1, 100 x), C: Adenocarcinoma with visible droplets of intracytoplasmic mucus (HE, 400 x), D: Squamous cell carcinoma (HE, 1000 x), E, F: Graphical illustration of EGFR gene mutations: exon 21 substitution (L858R) and exon 19 deletion (E746_A750) respectively, G, H: FISH positive results: amplification (1000 x) and high polysomy (600 x)].
Figure 2
Figure 2
The contribution of EGFR mutations types (in brackets: exon).
Figure 3
Figure 3
The influence of gender, FISH result and histologic type on EGFR mutation increase.
Figure 4
Figure 4
Frequency of EGFR gene mutations in NSCLC - European countries [listed: first author/year of publication/number of tested cases; based on literature review].
See this image and copyright information in PMC

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