Infiltrative tumour growth pattern correlates with poor outcome in oesophageal cancer

Abstract

Objective Oesophageal cancer (OEC) is an aggressive disease with a poor survival rate. Prognostic markers are thus urgently needed. Due to the demonstrated prognostic value of histopathological growth pattern (HGP) in other cancers, we performed a retrospective assessment of HGP in patients suffering from invasive OEC. Design A first cohort composed of 89 treatment-naïve operated patients with OEC from The Cancer Genome Atlas (TCGA) public database was constituted, from which H&E images and RNA-sequencing data were retrieved. Next, a second cohort composed of 99 patients with OEC treated and operated in a Belgian hospital was established. H&E-stained sections and extracted tumorous RNA were obtained from the samples. HGP were assessed on H&E slides as infiltrative (IGP) or expansive (EGP). TCGA RNA-sequencing data were analysed through the gene set enrichment analysis and Cytoscape softwares. Real-time quantitative PCR (qPCR) experiments were performed to assess gene expression in the Belgian cohort. Results IGP patients displayed a grim prognosis compared with EGP patients, while IGP was found as associated with numerous lymphovascular emboli and perinervous infiltrations. Analyses of the TCGA expression data showed that angiogenesis, epithelial-to-mesenchymal transition (EMT) and inflammation were significantly upregulated in IGP compared with EGP samples. qPCR experiments of three genes appearing as highly upregulated in each pathway showed no difference in expression according to the HGP. Conclusion The current study demonstrates the poor prognostic value carried by IGP in OC and suggests angiogenesis, EMT and inflammation as key carcinogenetic pathways upregulated in this pattern.