Abstract

Abstract Purpose To evaluate investigate the prognostic role of fibroblast growth factor receptor 1 (FGFR1) amplification in patients with surgically resected esophageal squamous cell carcinoma (ESCC). Patients and methods Gene copy number of FGFR1 was investigated in microarrayed tumors from 549 patients with ESCC who underwent curative esophagectomy. Gene copy number was evaluated by fluorescent in situ hybridization, and an FGFR1 amplified tumor (FGFR1 amp+) was prespecified if one of the following criteria is fulfilled: (I) FGFR1/centromer 8 (CEN8) ration is ≥ 2.0, (II) average gene copy nucleus is ≥ 6.0, and (III) percentage of tumor cells containing ≥ 15 gene copies or large cluster is ≥ 10%. Results FGFR1 amplification was detected in 8% (44 of 549) of ESCC. The average copy number per nucleus was 2.7 (range, 0-15.5) and the mean FGFR1/CEN8 ratio was 2.2 (range, 0-6). The 5-year disease free survival of the FGFR1 amp+ group was significantly shorter compared with that of the FGFR1amp- group (38.8% vs 63.7% P=0.012). In Cox proportional hazard model, patients with FGFR1 amp+ had a significantly greater risk of recurrence compare to amp- group after adjusting for sex, smoking status, pathologic stage, histology, and adjuvant chemotherapy (HR 1.74; 95% CI, 1.10-2.76, P=0.018). Of note, there was a trend toward worse overall survival for FGFR1 amp+ group compare to amp- group (5-year OS 32.0% vs 50.8%, P=0.11). FGFR1 amp+ group was significantly more likely to be smokers than FGFR1amp- group (97.7 % vs 2.3%, P=0.001). With increment of total cigarette smoking dosage, the incidence of FGFR1 amp+ significantly increased (P trend=0.005). Conclusions FGFR1 amplification is an independent prognostic factor for recurrence in surgically resected ESCC. FGFR1 amplification may have potential clinical application to the development of novel therapeutic strategies for ESCC Citation Format: Hyo Song Kim, Seung Eun Lee, Yoon Sung Bae, Joo Hang Kim, Hye Ryun Kim, Dae Joon Kim, Hyunki Kim, Yoon-La Choi, Byoung Chul Cho. Fibroblast growth factor receptor 1 gene amplification as an independent prognostic factor for recurrence in patients with resected squamous cell esophageal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2856. doi:10.1158/1538-7445.AM2014-2856

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