J Cancer 2020; 11(16):4691-4699. doi:10.7150/jca.44476 This issue Cite
Research Paper
1. Graduate School, WenZhou Medical University, Wenzhou, 325035, P.R. China.
2. Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (lung and esophagus), Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, 310022, P.R. China.
3. Department of Thoracic Medical Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, 310022, P.R. China.
#These authors contributed equally to this work.
Purpose: Fibroblast growth factor receptor 1 (FGFR1) alterations have been described in many cancers, including lung cancer, but the role has not been elucidated specifically in small cell lung cancer (SCLC). The present study aimed to identify the frequency of FGFR1 alterations among Chinese patients with surgically resected SCLC and the association with the clinicopathological characteristics and the survival were also investigated.
Methods: FGFR1 protein expression, FGFR1 amplification, FGFR1 mutations, and messenger RNA (mRNA) levels, were determined by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR), respectively in primary tumors from 33 patients with resected SCLC.
Results: 7/33(21.2%) of the specimens were positive for FGFR1 protein expression. FGFR1 amplification was identified in 4/28 cases (14.3%). If the cut-off value was determined to be 3.5, FGFR1 mRNA positivity was considered in 7/33 cases (21.2%). However, no mutation was detected in the 33 SCLC postoperative tissue specimens. No significant association was observed between FGFR1 protein expression or amplification and clinicalcharacteristics or prognosis. There was a distinct trend for mRNA level and poor prognosis, including recurrence-free survival (RFS) (p = 0.07) and overall survival (OS) (p= 0.08), but they did not reach statistical significance.
Conclusions: As novel FGFR1-targeted therapies are developed, FISH, IHC, especially mRNA were detected, which should be considered as biomarkers of FGFR1 pathway dysregulation in SCLC.
Keywords: small cell lung cancer (SCLC), FGFR1, mRNA expression, amplification, protein expression, mutation, prognosis