EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry

Abstract

BackgroundScreening mutations in epidermal growth factor receptor (EGFR) to analyze non-small-cell lung cancer (NSCLC) profile is the criterion to choose the best therapeutic strategy.New Oncology guidelines recommend EGFR mutation analysis before prescribing tyrosine kinase inhibitors (TKIs) treatment.Majority of lung cancer patients are diagnosed at advanced stages and generally only small biopsies materials are available for diagnostic and molecular characterization. The aim of this first work is to screen EGFR mutation status in Tunisian NSCLC by mutation-specific immunohistochemistry (IHC) and molecular biology, to estimate the relevance of proposing TKIs as a new therapeutic line.MethodsE746-A750 deletion and L858R mutations were screened in 50 unselected NSCLC formalin-fixed paraffin-embedded (FFPE) tissue samples. Mutation expression by IHC was evaluated by intensity and percentage of staining and correlated to patients’ data. DNA was extracted and EGFR mutations were analyzed by Sanger sequencing. Positive and negative controls were included for EGFR mutations in order to support the results.ResultsAmong our patients (48 men and 2 women) all adenocarcinoma (confirmed by histology and IHC with TTF1/Napsin A), 94% were smokers exceeding the tobacco risk threshold (at least 25 pack-years) and the women were none. 44% had EGFR mutation by IHC: 26% had simple mutation and 18% had concurrent mutation. All mutated cases were smokers except a woman who was none. Concurrent mutations patients exceeded 40 pack-years. 91.4% of IHC results were validated by molecular analysis (100% of negative and 85% of positive cases) showing either T > G (exon 21) or 2235–2249 del (exon 19).ConclusionsThese preliminary results confirm the usefulness of IHC to detect EGFR mutations but the frequency of concurrent mutations doesn’t appear in favor of EGFR TKIs treatment. In fact, literature reports a significantly worse response compared to those with single mutation when treated by TKIs.

Analysis of EGFR Mutation Status in Algerian Patients with Non-Small Cell Lung Cancer

“…Similarly, Arfaoui et al, (2018) reported 11,5% EGFR mutations. Nevertheless, Mraihi et al, (2018) found a frequency of 44% in a cohort of Tunisian patients using mutation-specific immunohistochemistry, which was in line with our results. Studies conducted in Arab countries reported frequencies ranging from 8.5-12% for Lebanon (Fakhruddin et al, 2014;Naderi et al, 2015), 15,6% for the Levant region (Tfayli et al, 2017), and up to 28.7 for the Gulf region (Jazieh et al, 2015).…”

Analysis of Genetic Alterations in Tunisian Patients with Lung Adenocarcinoma

“…The most common EGFR mutations associated with NSCLC (E746-A750 del and L858R), which together accounted for 86–90% of the total number of EGFR mutations (45% for E746-A750 del and 40–45% for L858R) [31,32,33], were investigated in 24 patients using IHC (Table 1). Abnormal immunolabeling of EGFR was detected in only one (4.16%) case, in contrast to the much higher incidence (44%) recently reported by Mraihi et al in 50 Tunisian patients [34]. In this context, doing a molecular verification by Sanger sequencing, after performing IHC, would be ideal for the positive case.…”

Management of lung cancer in Africa: Underdiagnosis and poor access to treatment – A close look at Nigeria and West African Sub-region

“…[22] Data from Egypt, Tunisia, and Morocco indicated higher frequency of P53 genetic mutation in lung cancer among North Africans though EGFR and MMP-3 mutations share similarities to their neighboring European countries. [39][40][41][42][43][44][45] However, genetic studies from North Africa cannot be extrapolated to all Africans since the people of North Africa are a genetically diverse, complex and heterogeneous population consisting of an admixture of Middle East Arabs, sub-Saharan Africans (SSAs), European, and autochthonous North Africans. [46,47] Cigarette smoking is one of the most studied non-genetic or modifiable lung cancer risk factors in Africans.…”