title: Amplification of Cyclin L1 is associated with lymph node metastases in head and neck squamous cell carcinoma (HNSCC).
abstract: Overrepresentation of chromosomal bands 3q25-q29 has been associated with shortened disease-specific survival in head and neck squamous cell carcinoma (HNSCC). To assess the prevalence of copy number gains (>4 signals per cell) and high-level amplifications (>8 signals per cell) from putative oncogenes in this chromosomal region (CCNL1, SNO, PIK3CA, TP73L), tissue microarray analysis was applied on 280 HNSCCs by fluorescence in situ hybridization. Overall frequency of additional copy numbers was 34.3% for CCNL1, 31.8% for SNO, 39.0% for PIK3CA and 38.3% for TP73L, respectively. In general, gains were more frequently detected in stage IV compared to stage I-III tumours. Performing multivariate logistic regression analysis, a significant association of CCNL1 gains and the presence of lymph node metastases was found, which was independent of anatomical site and T-stage of the primary tumour (P=0.049). Site-specific subgroup analysis further showed that copy number gains of CCNL1 and SNO occurred more frequently in oral carcinomas in advanced clinical stages as compared to N0 oral lesions (CCNL1: P=0.03; SNO: P=0.03). Finally, Kaplan-Meier analysis revealed that high-level amplifications of CCNL1 correlated with shorter overall survival of the patients. Our results indicate that CCNL1 plays a critical role in the loco-regional progression of HNSCC and may serve as an indicator for occult advanced tumour stages.
authors.affiliation: Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Sticht
authors.forename: C
authors.initials: C
authors.lastname: Hofele
authors.forename: C
authors.initials: C
authors.lastname: Flechtenmacher
authors.forename: F X
authors.initials: FX
authors.lastname: Bosch
authors.forename: K
authors.initials: K
authors.lastname: Freier
authors.forename: P
authors.initials: P
authors.lastname: Lichter
authors.forename: S
authors.initials: S
authors.lastname: Joos
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D016213:Cyclins / Q000235:genetics*; D018572:Disease-Free Survival; D005784:Gene Amplification; D005819:Genetic Markers; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016015:Logistic Models; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C468873:CCNL1 protein, human; D016213:Cyclins; D005819:Genetic Markers