Evidence for frequent concurrent DCUN1D1, FGFR1, BCL9 gene copy number amplification in Squamous Cell Lung Cancer

7061 Background: SOX2 is a member of the SRY-related HMG-box family of transcription factors and has been shown to be frequently amplified and overexpressed in squamous cell lung cancer, with conflicting results regarding its prognostic relevance. Similarly, FGFR1, a transmembrane tyrosine kinase receptor belonging to the fibroblast growth factor receptor family, has been recently reported to be amplified in squamous cell lung carcinomas, suggesting a potential role for FGFR1 as a therapeutic target in NSCLC. Aim of the present study is to evaluate SOX2 and FGFR1 gene copy number in surgically resected NSCLCs, to investigate their prognostic relevance and their association with clinico-pathological characteristics. Methods: SOX2 and FGFR1 gene copy number was assessed by fluorescence in situ hybridization (FISH) in tissue microarray cores from 447 surgically resected NSCLCs. Each patient was given a score ranging from 1 to 6 according to increasing mean copy number per cell of each gene, with 6 indicating true gene amplification. Results: SOX2 and FGFR1 FISH was successfully performed in 445 patients (pts), which were grouped as + (score 5-6) and - (score 1-4). Using this scoring system 105 (23.6%) pts tested SOX2+, while 74 (16.6%) pts resulted FGFR1+. True gene amplification for SOX2 and FGFR1 was observed in 19 (4.3%) and 37 (8.3%) cases, respectively. SOX2+ and FGFR1+ status was significantly associated with squamous histology (p<.001). Additionally, SOX2+ pts had a significantly higher chance of being former/current smokers, male and FGFR1+. FGFR1 gene status had no prognostic impact in the whole population and in the squamous cell carcinoma subgroup. Conversely, SOX2+ pts had significantly longer overall survival compared with SOX2- pts (HR 0.68, p=.020). When restricting survival analysis to squamous cell histology, stage I-II SOX2+ pts had a significant survival advantage compared with SOX2- group (HR 0.38, p=.006), while no difference was observed in stage III-IV pts. Conclusions: Increased SOX2 and FGFR1 gene copy number is a common event in lung cancer pts with squamous cell histology. SOX2 gene gain is a favorable prognostic factor in surgically resected pts, particularly in early stage squamous cell cancers.

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FGFR1 amplification and EGFR mutation in Chinese squamous cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.7545 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 7545-7545

Author(s):

Zhigang Wei ◽

Jie Wang ◽

Hua Bai ◽

Tongtong An ◽

Zhijie Wang ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Gene Copy Number ◽

Squamous Cell Lung Cancer ◽

Egfr Mutations ◽

Gene Copy ◽

Clinicopathologic Characteristics ◽

Potential Biomarker

7545 Background: Squamous cell lung cancer (SCC) lacks for effective targeted therapies. FGFR1 amplification has emerged as a potential biomarker. This study aimed to explore clinicopathologic characteristics of FGFR1 amplification in Chinese SCC patients and further explore the correlation between FGFR1 amplification and EGFR mutations. Methods: One hundred seventy-seven SCC patients were included in this retrospective study. Gene copy number of FGFR1 and EGFR mutations were detected by fluorescence in situ hybridization (FISH) and denaturing high-performance liquid chromatography (DHPLC), respectively. Results: FGFR1 amplifications were detected in 24.9% (44/177) Chinese SCC patients. FGFR1 amplification in SCC was more common in male (28.0%, 40/143) and smokers (28.7%, 39/136) than female (11.8%, 4/34, p=0.049) and nonsmokers (12.2%, 5/41, p=0.032). FGFR1 amplification and EGFR mutations were mutually exclusive (p=0.006), fourty-one of 139(29.4%) patients with wild-type EGFR had FGFR1 amplification, while 3 of 38 (7.9%) patients with EGFR mutation had FGFR1 amplification. Conclusions: FGFR1 amplification was common in Chinese squamous cell lung cancer, and mutually exclusive with EGFR mutations.

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