Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Introduction</jats:p>
<jats:p>Stimulation of Fibroblast-growth-factor-receptor-1 (FGFR1) plays an important role in cell differentiation and cell growth. Amplification of the FGFR1 gene was described in various cancer types. Clinical phase I trials are currently performed to address the potential applicability of anti-FGFR1-drugs in squamous cell carcinoma of the lung. Prevalence and clinical significance of FGFR1 amplification are unknown in esophageal carcinoma.</jats:p>
<jats:p>Material and Methods</jats:p>
<jats:p>In this study, six hundred formalin-fixed paraffin-embedded tissue samples from patients with esophageal carcinoma were analysed, including 346 patients with adenocarcinoma and 254 patients with squamous cell carcinoma. Dual-labeling Fluorescence in situ hybridization (FISH) was applied using probes for FGFR1 and centromere 8. The initial analysis was in a tissue microarray (TMA) format. All available tumor blocks from amplified tumors were subsequently analysed for heterogeneity on large sections. When available, lymph node metastases and tumor-adjacent dysplasia were also analysed on large sections from these tumors,</jats:p>
<jats:p>Results</jats:p>
<jats:p>FGFR1 amplification was more frequently seen in squamous cell carcinoma (9.4% of 202 interpretable cases) than in adenocarcinoma (1.6% of 308). High polysomy was found in an additional 5.9% of squamous cell carcinoma and 0.6% of adenocarcinoma. FGFR1 amplification was significantly associated with histologic grade (p=0.02) but was unrelated to tumor type, pT, pN, pM, UICC stage and survival. FGFR1 amplification was homogeneous across the tumor in most cases. FGFR1 heterogeneity was observed in only 3 of 24 cases. FGFR1 amplification was similarly observed in the primary tumor and in 6 cases each of lymph node metastases and dysplasia.</jats:p>
<jats:p>Summary</jats:p>
<jats:p>In conclusion, FGFR1 amplification in squamous cell carcinoma of the esophagus occurs at similar frequencies as in squamous cell carcinoma of the lung. The high homogeneity of FGFR1 in the primary tumor and the lack of discordant results in dysplasia argue for FGFR1 amplification, representing an early alteration in a subgroup of esophageal cancers. The high homogeneity of FGFR1 amplification provides further arguments for FGFR1 representing an interesting drug target in these cancers.</jats:p>
<jats:p>Citation Format: Katharina von Loga, Jule Kohlhaussen, Andreas H. Marx, Guido Sauter, Tobias Grob, Alexander Quaas. FGFR1 amplification is linked to the squamous cell carcinoma subtype in esophageal carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3024. doi:10.1158/1538-7445.AM2013-3024</jats:p>