Table 1.
Main characteristics and results of the eligible studies
| First author (references) | Year | Country | Cancer type | Stage | Patient number | Median age, years (range) | Detection method | Cutoff value | Positive rate (%) | Clinicopathological features | HR estimation | HR for overall survival (95% CI) | HR for disease-free survival (95% CI) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seo et al28 | 2014 | Korea | NSCLC | I–III | 369 (AC 230, SCC 139) | 65 (21–84) | FISH | FGFR1 gene copy number ≥6.2 | 32/369 (8.7%) | G, C, LN, S, H | HR | SCC: 1.79 (0.83–3.87) | SCC: 1.63 (0.87–3.07) |
| Cihoric et al8 | 2014 | Switzerland | NSCLC | I–II | 329 (SCC 169, AC 137, LCC 23) | 66.9 (42–83) | FISH | FGFR1/CEP8 signal ratio ≥2.0 | 41/329 (12.5%) | G, C, T, H | HR | NSCLC: 2.06 (1.05–4.05); SCC: 1.05 (0.57–1.93) | NSCLC: 1.46 (0.76–2.81); SCC 1.12 (0.48–2.58) |
| Wynes et al15 | 2014 | Poland | NSCLC | I–IV | 189 (AC 55, SCC 103, LCC 5, Other 26) | 64 (37–85) | SISH | FGFR1 gene copy number ≥4, or FGFR1:CEP8 ratio ≥2 | 14/182 (8%) | A, G, C, S, D, H | HR | 0.99 (0.50–1.96) | NA |
| Russell et al16 | 2014 | Australia | NSCLC | I–IV | 338 (AC 99, SCC 178, LCC 41, Other 20) | 69 (19–87) | FISH | High FGFR1 amplification: FGFR1/centromere 8 (CEN8) ≥2, or the tumor cell percentage with ≥15 FGFR1 signals ≥10%, and the average number of FGFR1 signals/tumor cell nucleus ≥6; Low FGFR1: tumor cell percentage with ≥5 FGFR1 signals ≥50% | 49/352 (13.9%) | H | HR | NSCLC: 1.09 (0.72–1.66); SCC: 1.01 (0.65–1.58) | SCC: 1.04 (0.67–1.60) |
| Toschi et al17 | 2014 | Italy | NSCLC | I–IV | 447 (AC 244, SCC 138, Other 65) | 66 (33–86) | FISH | Gene copy gain: ≥4 gene copies/cell; | Amplification: | G, C, S, H# | Survival curve | 0.99 (0.70–1.40) | NA |
| Serizawa et al18 | 2014 | Japan | AC | I–IV | 411 | 68 (29–89) | qPCR | Amplification: presence of gene clusters | 37/445 (8.3%); Copy-number gain 37/445 (8.3%) | ||||
| Pros et al19 | 2013 | Spain | NSCLC | I–IV | 265 (AC 86, SCC 150, LCC 26, Other 3) | NA | FISH | The ratio of the normalized quantity of FGFR1/COL8A1 ≥2 | 2/411 (0.05%) | C | – | NA | NA |
| Gadgeel et al9 | 2013 | US | NSCLC | I–IV | qPCR | FGFR1 copy-number >12 or presence of gene clusters | 17/265 (6%) | G, C, H | – | NA | NA | ||
| (Training cohort) | 203 (AC 98, SCC 79, LCC 15, Other 11) | 66.2 (35.0–83.8) | FGFR1 exon 15 copy-number value >3.50 | G, H | HR | ||||||||
| (Validation cohort) | 142 (AC 71, SCC 57, LCC 13, Other 1) | 65.2 (25.8–81.9) | 12/203 (5.9%) | 2.19 (1.02–4.75) | NA | ||||||||
| Craddock et al20 | 2013 | Canada | SCC | I–IV | 135 | 69.2 (44.0–83.9) | FISH | 5/142 (3.5%) | 2.91 (1.14–7.41) | NA | |||
| Tran et al21 | 2013 | Australia | NSCLC | I–III | 264 (AC 115, SCC 101, LCC 44, Other 4) | 66.5 (57.8–75.2) | Dual-color FISH | FGFR1 copy number ≥5.0 | 22/121 (18.2%) | G, C, S | HR | 1.33 (0.67–2.62) | 1.15 (0.59–2.25) |
| Kim et al7§ | 2013 | Korea | SCC | I–III | 262 | 66 (36–81) | FISH | Amplification: FGFR1/CEP8 ≥2.0, or mean FGFR1 signals per tumor cell ≥6.0, or percentage of tumor cells or containing FGFR1 clusters ≥10%; FGFR1 copy-number gain: the mean of FGFR1 signals was between 4 and 6 or at least 50% of counted cells contained ≥4 FGFR1 signals | Amplification: 37/264 (14%); Copy-number gain 12/264 (4.5%) | G, C, S, D, H# | Survival curve | 1.29 (0.85–1.95) | NA |
| Heist et al22 | 2012 | US | SCC | I–IV | 226 | 69 (38–91) | FISH | High amplification: FGFR1/CEP8 ≥9.0; | High amplification: | G, C, LN, S, H | HR | 1.83 (1.15–2.89) | 2.24 (1.45–3.45) |
| Kohler et al23 | 2012 | Germany | NSCLC | I–IV | 236 (AC 64, SCC 133, LCC 4, Other 35) | NA | FISH | Low amplification: FGFR1/CEP8 >2 and <9 | 34/262 (13.0%); Low amplification: 105/262 (40.1%) | ||||
| Schildhaus et al24 | 2012 | Germany | NSCLC | NA | 420 (AC 100, SCC 307, Other 13) | NA | FISH | FGFR1/CEP8 ≥2.2 | 37/226 (16%) | G, C, S | Survival curve | 0.84 (0.53–1.33) | NA |
| Zhang et al25 | 2012 | People’s Republic of China | NSCLC | I–IV | 127 (AC 76, SCC 48, Other 3) | NA | FISH | FGFR1 copy-number ≥4 | 14/133 (10.5%) | G, H | – | SCC: 2.64 (1.43–4.86) | NA |
| Sasaki et al10 | 2012 | Japan | SCC | I–IV | 100 | NA (29–86) | qPCR | FGFR1/CEN8 ≥2.0 or FGFR1 signals/cell nucleus ≥6 or the percentage of tumor cells containing ≥15 FGFR1 signals or large clusters is ≥10% or the percentage of tumor cells containing ≥5 FGFR1 signals is ≥50% | 58/290 (20%) for SCC, 0/97 (0%) for AC, 2/13 (15.4%) for others | H | – | NA | NA |
| Weiss et al26 | 2010 | US and Switzerland | NSCLC | NA | 232 (AC 77, SCC 155) | NA | SNP array | FGFR1/CEP8 ≥2.0 or cluster signals ≥10% of tumor cells | 11/127 (8.7%) | G, C, S, LN, H | – | NA | NA |
| Dutt et al27 | 2011 | US | NSCLC | I–IV | 628 (AC 555, SCC 46, Other 27) | NA | SNP array | FGFR1 gene copy number >4 | 32/100 (32%) | G, C, S, D, LN, H | – | 1.48 (0.57–3.86) | NA |
| Chromosome 8p12 that included FGFR1 ≥4 copies | AC, 1/77 (1.3%); SCC, 15/115 (9.7%) | C, H | Survival curve | 1.19 (0.78–1.81)*,† | NA | ||||||||
| Log2 ratio >0.7 or 3.25 normalized DNA copies | 32/628 (5.96%) | A, S, D, H | – | NA | NA |
Notes:
#
FGFR1–positive (included FGFR1 amplification and copy-number gain);
§
high amplification vs not high amplification;
†
HR FGFR1 copy number >9 vs copy number =2;
*
only includes SCC patients.
Abbreviations: HR, hazard ratio; CI, confidence interval; NSCLC, non-small-cell lung cancer; AC, adenocarcinoma; SCC, squamous cell carcinoma; LCC, large cell carcinoma; FISH, fluorescence in situ hybridization; SISH, silver ISH; qPCR, quantitative polymerase chain reaction; SNP, single-nucleotide polymorphism; G, sex; C, smoking status; S, stage; D, histologic differentiation; H, histology; LN, lymph-node metastasis; P, performance status; NA, not available; T, tumor size; A, age.