Recurrent FCFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC)

• Published in: Oral oncology 2007-01, Vol.43 (1), p.60-66
• Main Authors: Freier, K, Schwaenen, C, Sticht, C, Flechtenmacher, C, Muhling, J, Hofele, C, Radlwimmer, B, Lichter, P, Joos, S
• Format: Article
• Language: English
• ISSN: 1368-8375
• DOI: 10.1016/j.oraloncology.2006.01.005

Chromosomal aberrations are known to have an impact on the initiation and progression of oral squamous cell carcinoma (OSCC), but individual genes involved in OSCC patho-genesis are poorly described. To elucidate the molecular events underlying oral carcinogenesis, a set of primary OSCC were screened for distinct genetic imbalances by means of array-based comparative genomic hybridisation. For this, a DNA array was used containing 812 genomic targets including oncogenes, tumour-suppressor genes and chromosomal regions frequently altered in human neoplasms. The most frequent aberrations were amplification of MYC, EGFR, CCND1 and PIK3CA, whereas deletions affected TRAILR1 and ATM. Furthermore, a distinct high-level amplification of the fibroblast growth factor receptor 1 (FGFR1) locus was detected in two cases. Detailed FISH analysis on OSCC tissue microarray sections revealed amplification prevalence for FGFR1 of 17.4% (16/92). Furthermore, FGFR1 protein analysis by immunohisto-chemistry on a TMA containing 178 OSCC found a high FGFR1 expression in tumours of early t-stadiumand UICC stage (T1/2 vs. T3/4: p = 0.002; SI-II vs. S III-IV: p = 0.048). Our results indicate that an increase in FGFR1 expression contributes to oral carcinogenesis at an early stage of development.