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

Abstract Background Screening 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. Methods E746-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. Results Among 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). Conclusions These 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

First case report of Cohen syndrome in the Tunisian population caused by VPS13B mutations

Abstract Background Cohen syndrome is a rare autosomal recessive developmental disorder that comprises variable clinical features counting developmental delay, pigmentary retinopathy, myopia, acquired microcephaly, truncal obesity, joint hypermobility, friendly disposition and intermittent neutropenia. VPS13B (vacuolar protein sorting 13, yeast, homologue of B) gene is the only gene responsible for Cohen Syndrome, causative mutations include nonsense, missense, indel and splice-site variants. The integrity of the Golgi apparatus requires the presence of the peripheral membrane protein VPS13B that have an essential function in intracellular protein transport and vesicle-mediated sorting. Case presentation In this study, we performed whole exome sequencing (WES) in a Tunisian family with two young cases having developmental delay, hypotonia, autism spectrum disorder, ptosis and thick hair and eyebrows. The proposita presented also pigmentory retinopathy. Compound heterozygous mutation in VPS13B gene was detected by WES. This mutation inherited from healthy heterozygous parents, supports an unpredictable clinical diagnosis of Cohen Syndrome. The proband’s phenotype is explained by the presence of compound heterozygous mutations in the VPS13B gene. This finding refined the understanding of genotype-phenotype correlation. Conclusions This is the first report of a Tunisian family with Cohen syndrome mutated in the VPS13B gene

Epidemiological, clinical, and bacteriological findings among tunisian patients with tuberculous cervical lymphadenitis

International audienceThe incidence of tuberculous cervical lymphadenitis (TCL) is likely to be on the rise in Tunisia over the last two decades. However, this pathological condition remains poorly characterized, in regard to involved mycobacterial species. Purpose: To study the etiology and treatment outcome of TCL among Tunisian patients; to indicate the myc-obecteria responsible for the majority of TCL cases. This prospective study has involved 114 patients, clinically diagnosed as TCL, presenting to a National referral hospital in Tunis, from November 2011 to January 2014. Results: 69 patients displayed typical cytological signs of TCL, whose mycobacterial etiology was confirmed in 23 cases. 4 cases may be a possible disseminated TB. Mycobacterial species assignment could be established for 15 culture-positive specimens, 11 of which were found to be Mycobacterium bovis, while the remaining were identified as tuberculosis. 6 of M. bovis isolates belonged to the BOVIS1 spoligopattern, and 3 of the M. tuberculosisisolates to the Haarlem3, one of the most prevalent genotype associated with pulmonary tuberculosis in Tunisia. Although all subjects lived in an urban area, the majority declared having consumed raw milk and derived products. The cure rate was low, as among patients that completed an anti-tubercular chemotherapy of at least 8 months, only 55.5% were cured. Conclusion: Our results are consistent with literature since positive cases demonstrated by AFB smear test don't exceed 37.4% and varied by culture between 19 and 71%. This is the first indication that M. bovis is a significant cause of TCL in Tunisia. Consumption of unpasteurized dairy products is the most likely source of transmission. The low cure rates among TCL cases should call health authorities for improved management and therapeutic schemes