Amplification of FGFR1 gene and expression of FGFR1 protein is found in different histological types of lung carcinoma.

Although lung cancer continues to be the leading cause of cancer-related death, accurate diagnosis followed by personalized treatment is expected to raise the 5-year survival rate. Targeted therapies are now in routine clinical use, in particular for lung adenocarcinoma (ADC). Fibroblast growth factor receptor 1 (FGFR1) has recently emerged as a molecular target, especially in squamous cell/epidermoid carcinoma (SQC) of the lung. This paper evaluates FGFR1 expression and gene copy number in adenocarcinomas, squamous cell carcinomas, pleomorphic carcinomas (PLEOMC) and adenosquamous carcinomas (ADSQC) of the lung and also explores the epithelial-mesenchymal transition (EMT) pathway. We studied 76 lung carcinomas: 34 ADC, 24 SQC, 10 PLEOMC and 8 ADSQC. FGFR1 expression was evaluated by immunohistochemistry and gene amplification by fluorescence in situ hybridization (FISH). Higher FGFR1 protein expression was observed in all tumour types compared to non-tumour tissue. FGFR1 expression was higher in ADC and PLEOMC than in SQC. We found a tendency to higher expression in ADC than in SQC and significantly higher expression in PLEOMC than in other histological subtypes. FISH-based amplification of FGFR1 was identified in 15 (20 %) lung carcinomas: 5 (15 %) ADC, 5 (21 %) SQC, 3 (30 %) PLEOMC and 2 (25 %) ADSQC. Amplification was more frequent in SQC without significant differences. FGFR1 protein is expressed in the majority of lung carcinomas, though it is higher in ADC and PLEOMC (the latter may reflect the importance of FGFR1 control of the EMT pathway). FGFR1 amplification was identified in all types of lung carcinoma. Although FGFR1 is most frequently amplified in SQC, other histological types merit assessment of FGFR1 amplification, in order to select patients that might benefit from targeted therapy.

Association Between IL-4 and IL-6 Expression Variants and Gastric Cancer Among Portuguese Population.

INTRODUCTION: Multiple studies have reported strong associations between Helicobacter pylori (Hp) inflammation and gastric cancer (GC) development. Altered expressions of pro/anti-inflammatory cytokines have a crucial role in Hp and GC proliferation. Although there are many studies related to cytokines polymorphisms involvement in GC risk, the role of Interleukin-4 (IL-4) and Interleukin-6 (IL-6) in gastric inflammation process is not yet clarified. AIM: This study aimed to investigate the impact of common IL-4 and IL-6 polymorphisms in GC development risk among Portuguese population. METHODS: A total of 100 GC biopsies (50 with intestinal type, IGC, 50 with diffuse type, DGC) and 50 chronic gastritis cases, used as control group, were included in this case-control study. IL-4 and IL-6 common polymorphisms were genotyped by PCR-SSP, using commercially available kits. RESULTS: IL-4 low producer genotypes, IL-4-590TT (OR = 6.7; 95% CI 1.4-32.4) and IL-4-1098GG (OR = 4.4; 95% CI 1.7-16.9) were found associated with IGC and DGC, respectively. We also verified that IL-4 TTT haplotype was linked with both IGC (OR = 5.8; 95% CI 2.3-14.4) and DGC (OR = 2.3; 95% CI 1.0-5.5) groups. Concerning IL-6 results, IL-6-174CG genotype showed a higher prevalence among IGC cases (OR = 7.3; 95% CI 2.7-20.3), and IL-6-174CC (OR = 3.8; 95% CI 1.7-8.7) showed upper prevalence within DGC subjects. Finally, IL-6-174/nt565CG haplotype showed a significant association with both IGC (OR = 7.3; 95% CI 2.7-20.3) and DGC (OR = 7.9; 95% CI 4.2-14.9). CONCLUSION: IL-6 and IL-4 expression variants seem to have an important role in GC risk mechanisms. This study provides preliminary evidence that IL-4 and IL-6 polymorphisms, although not directly linked to the disease, may be useful tools in the study of this multifactorial disease.

INTRODUÇÃO: Múltiplos estudos têm referenciado fortes associações entre infeção/inflamação por Helicobacter pylori (Hp) e o desenvolvimento do cancro gástrico (CG). A alteração na expressão das citocinas pro/anti-inflamatórias desempenha um papel crucial na proliferação da Hp e do CG. Apesar de existirem vários estudos relacionados com os polimorfismos das citocinas envolvidos na progressão do CG, o papel da Interleukin-4 (IL-4) e Interleukin-6 (IL-6) no mecanismo de inflamação gástrica ainda não está totalmente esclarecido. OBJETIVO: Este estudo teve como objetivo principal estudar o impacto dos polimorfismos comuns da IL-4 e IL-6 no risco de desenvolvimento do CG na população Portuguesa. MÉTODOS: Um total de 100 biópsias de CG (50 do tipo intestinal, CGI, 50 do tipo difuso, CGD) e 50 casos de gastrite crónica, utilizados como grupo controlo, foram incluídos neste estudo de caso-controlo. Os polimorfismos da IL-4 e da IL-6 foram genotipados por PCR-SSP, utilizando kits comerciais disponíveis. RESULTADOS: Os genótipos de baixa produção da IL-4, IL-4 -590TT (OR = 6,7; 95% CI 1,4 a 32,4) e IL-4 -1098GG (OR = 4,4; 95% CI 1,7 a 16,9) encontram-se associados com o CGI e com o CGD, respetivamente. Também verificámos que o haplótipo IL-4 TTT encontra-se relacionado com ambos os grupos de CGI (OR = 5,8; 95% CI 2,3 a 14,4) e CGD (OR = 2.3; 95% CI 1,0 a 5,5). Considerando os resultados da IL-6, o genótipo IL-6-174CG apresentou uma elevada prevalência entre os pacientes com CGI (OR = 7,3; 95% CI 2,7 a 20,3), e o IL-6 -174CC (OR = 3,8; 95% CI 1,7 a 8,7) apresentou maior prevalência no grupo de CGD. Finalmente, o haplótipo IL-6 -174/nt565CG apresentou uma associação significativa com ambos os grupos de CGI (OR = 7,3; 95% CI 2,7 a 20,3) e CGD (OR = 7,9; 95% CI 4,2 a 14,9). CONCLUSÃO: Os variantes de expressão da IL-6 e IL-4 parecem desempenhar um papel importante nos mecanismos de progressão do CG. Este estudo fornece evidências preliminares de que os polimorfismos da IL-4 e da IL-6, apesar de não estarem diretamente ligados a esta patologia, podem ser ferramentas úteis no estudo desta doença multifatorial.