<i>FGFR1</i> Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell Carcinoma Subtype in Esophageal Carcinoma

<div><p>Background and Aims</p><p>Amplification of the <i>fibroblast growth factor receptor 1</i> (<i>FGFR1</i>) is believed to predict response to multi-kinase inhibitors targeting <i>FGFR1</i>. Esophageal cancer is an aggressive disease, for which novel targeted therapies are highly warranted.</p><p>Methods</p><p>This study was designed to investigate the prevalence and clinical significance of <i>FGFR1</i> amplification in a tissue microarray containing 346 adenocarcinomas and 254 squamous cell carcinomas of the esophagus, using dual-labeling fluorescence <i>in situ</i> hybridization (FISH) analysis.</p><p>Results</p><p><i>FGFR1</i> amplification, defined as a ratio of <i>FGFR1</i>:centromere 8 copy numbers ≥ 2.0, was more frequently seen in squamous cell carcinoma (8.9% of 202 interpretable cases) than in adenocarcinoma (1.6% of 308; p<0.0001). There was no association between <i>FGFR1</i> amplification and tumor phenotype or clinical outcome. To study potential heterogeneity of <i>FGFR1</i> amplification, all available tumor blocks from 23 <i>FGFR1</i> amplified tumors were analyzed on conventional large sections. This analysis revealed complete homogeneity of <i>FGFR1</i> amplification in 20 (86.9%) primary tumors and in all available lymph node metastases. Remarkably, <i>FGFR1</i> amplification was also seen in dysplasia adjacent to tumor in 6 of 9 patients with <i>FGFR1</i> amplified primary cancers.</p><p>Conclusions</p><p>In conclusion, <i>FGFR1</i> amplification occurs in a relevant subgroup of carcinomas of the esophagus and may play a particular role for development of squamous cell cancers. The high homogeneity of <i>FGFR1</i> amplification suggests that patients with <i>FGFR1</i> amplified esophageal cancers may particularly benefit from anti-<i>FGFR1</i> therapies and prompt for clinical studies in this tumor type.</p>