E75

Ulricke Bockmühl

Dept. of Otorhinolaryngology, Humboldt-Univ., Berlin, Germany

Introduction: In head and neck squamous cell carcinomas (HNSCC) the prognostic factors that are routinely considered when deciding therapeutic strategies are still stage and site of the primary tumour, and the presence of nodal or distant metastases. However, it is recognized that these clinical predictors are limited since they do not satisfactorily reflect the biological behaviour of the individual tumour. With the evolving understanding of the genetic and molecular basis of human malignancies, there are an increasing number of factors being claimed to provide prognostic information even in HNSCC.

Material & Methods: We review the work on potential molecular cytogenetic biomarkers relevant to HNSCC and the current status of these molecular markers since carcinogenesis is the result of chromosomal alterations driving to molecular genetic changes. We also present our results searching for genetic alterations related to metastasis and clinical outcome in HNSCC, e.g. using special molecular cytogenetic analysis we evaluated 113 primary HNSCC and 38 lymph node metastases (LNM). The analysis enabled the assessment of the clonal relationship between primary tumor and LNM, the identification of genetic lesions that determine the metastastic phenotype of HNSCC and those that are responsible for the patient’s survival.

Results: In particular, the deletions of chromosomes 10q, 11q and 14q were of statistical significance for the development of LNM. Kaplan-Meier analysis and multivariate Cox proportional hazards regression models consistently identified the gains of chromosomes 3q21-29, 11q13 and the loss of chromosomes 8p21-22 as independent prognostic markers. In addition, these 3 markers allowed a molecular dissection of the patients with low clinical risk (pN0 and pT2 tumors).

Conculsions: Thus, the genomic data enabled a stratification of the patients into subgroups with different clinical course highlighting the necessity of a genetically based tumor classification for refining diagnosis and treatment of HNSCC patients.