Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2016; 22(44): 9803-9812
Published online Nov 28, 2016. doi: 10.3748/wjg.v22.i44.9803
Prognostic implications of FGFR1 and MYC status in esophageal squamous cell carcinoma
Dohee Kwon, Ji Yun Yun, Bhumsuk Keam, Young Tae Kim, Yoon Kyung Jeon
Dohee Kwon, Ji Yun Yun, Yoon Kyung Jeon, Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea
Bhumsuk Keam, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea
Young Tae Kim, Department of Thoracic Surgery, Seoul National University Hospital, Cancer Research Institute, Genomic Medicine Institute, Seoul National University College of Medicine, Seoul National University College of Medicine, Seoul 03080, South Korea
Author contributions: Kwon D and Yun JY contributed equally to this work; Kwon D and Yun JY collected and analyzed the data and wrote the manuscript; Keam B and Kim YT collected the clinical data; Jeon YK supervised and conducted the study; all authors have read and approved the final version of the manuscript.
Supported by the National Research Foundation for the Global Core Research Center, No. 2016005276; and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, No. HI14C0069.
Institutional review board statement: This study was reviewed and approved by Institutional Review Board of SNUH (H-1405-055-579).
Conflict-of-interest statement: The authors declare no conflict of interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yoon Kyung Jeon, MD, PhD, Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, South Korea. junarplus@chol.com
Telephone: +82-2-20721347 Fax: +82-2-7435530
Received: August 21, 2016
Peer-review started: August 24, 2016
First decision: September 5, 2016
Revised: September 20, 2016
Accepted: September 28, 2016
Article in press: September 28, 2016
Published online: November 28, 2016
Processing time: 97 Days and 1.9 Hours
Abstract
AIM

To investigate the clinicopathological features and prognostic implications of combined MYC and fibroblast growth factor receptor 1 (FGFR1) status in esophageal squamous cell carcinomas (ESCCs).

METHODS

All patients with ESCC (n = 180) underwent surgical resection at Seoul National University Hospital sometime between 2000 and 2013. A tissue microarray was constructed using cores obtained from representative tumor areas of formalin-fixed, paraffin-embedded tissue blocks. FGFR1 and MYC copy numbers were quantified using fluorescence in situ hybridization. The level of MYC expression was determined using immunohistochemistry. FGFR1 and MYC amplification status was compared between primary and metastatic lymph nodes. Univariate and multivariate survival analyses were performed according to adjuvant therapy status.

RESULTS

FGFR1 and MYC amplifications were observed in 21.4% (37/173) and 54.2% (91/168) of patients, respectively, while MYC expression was observed in 58.9% (106/180) of patients. There was a positive correlation between MYC amplification and overexpression (P = 0.002). Although FGFR1 amplification was not associated with MYC amplification or expression, 12.3% (20/163) of patients exhibited both FGFR1 amplification and MYC expression. There was also a correlation in FGFR1 amplification status between matched primary tumors and metastatic lymph nodes (P < 0.001). MYC expression was higher in ESCCs with pT1 (P < 0.001) and in those with no lymph node metastasis (P = 0.023). MYC expression was associated with prolonged disease-free survival (P = 0.036) and overall survival (OS) (P = 0.017) but was not an independent prognostic factor. FGFR1 amplification was an independent predictor for prolonged OS in all patients (P = 0.029) and in those who did not receive adjuvant therapy (P = 0.013). Combined FGFR1 amplification and MYC expression predicted better OS in patients who did not receive adjuvant therapy (P = 0.034) but not in those who did receive adjuvant therapy.

CONCLUSION

FGFR1 amplification and MYC expression have prognostic implications in resected ESCCs with respect to adjuvant therapy. The role of FGFR1-targeted therapy in ESCC remains to be explored.

Keywords: Receptor tyrosine kinase; Fibroblast growth factor receptor 1; MYC; Esophageal squamous cell carcinoma; Gene amplification; Prognosis; Fluorescent in situ hybridization

Core tip: MYC expression, together with fibroblast growth factor receptor 1 (FGFR1) amplification, was reported to modulate oncogenic transformation. We evaluated both FGFR1 and MYC statuses in patients with resected esophageal squamous cell carcinoma (ESCC). FGFR1 and MYC amplifications were observed in 21.4% and 54.2% of patients with ESCC, respectively, while 12.3% exhibited both FGFR1 amplification and MYC expression. MYC expression and FGFR1 amplification were significantly associated with prolonged survival. Combined FGFR1 amplification and MYC expression was a predictor of better survival in patients who did not receive adjuvant therapy, but not in those who did. As such, FGFR1 and MYC might have prognostic implications in resected ESCCs with respect to adjuvant therapy.