Prognostic factors in squamous cell carcinoma of the head and neck, with emphasis on 11q13 rearrangements and cyclin D1 overexpression

University dissertation from Dept. of Otorhinolaryngology/Head and Neck Surgery, University Hospital, S-221 85 Lund, Sweden

Abstract: At present, clinical outcome or response to therapy can not be fully predicted in individual cases of squamous cell carcinoma of the head and neck (SCCHN). The overall aim of the present studies was to investigate potential prognostic factors, more closely related to the malignant progression of a tumor than the established markers, such as the TNM-classification system. Tumor samples were investigated using cytogenetic analysis, immunohistochemistry (IHC), flow cytometry (FCM), slot blot hybridization, differential PCR and RT-PCR, and fluorescence in situ hybridization (FISH). The findings were compared with clinical data. Rearrangements of chromosome 11, band q13 (11q13), overexpression of the oncoprotein cyclin D1, complex karyotypes, and high histopathological malignancy scoring were all correlated to poor prognosis in SCCHN. They all yielded independent prognostic information in multivariate analysis. Cyclin D1 overexpression was correlated to partial or complete response to neoadjuvant chemotherapy. Chromosomal translocations of 11q13, together with genomic amplification, are involved in cyclin D1 oncogene (CCND1) deregulation, leading to cyclin D1 overexpression. Complex karyotypes are observed in DNA-diploid tumors, as assessed by FCM, partly explaining the low prognostic information yielded by this method in certain SCCHN. The present findings indicate 11q13 rearrange- ments and cyclin D1 overexpression, as assessed by cytogenetic analysis and IHC, respectively, to be new, independent prognostic factors in SCCHN. Furthermore, the latter parameter might predict response to induction chemotherapy. Cyclin D1 overexpression by IHC could easily be introduced to clinical work, in the hope that therapy will be brought a step closer to individualized treatment schedules.

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