Detection of Distinct Changes in Gene-expression Profiles in Specimens of Tumors and Transition Zones of Tenascin-positive/-negative Head and Neck Squamous Cell Carcinoma

Abstract

Background/Aim: Having previously initiated genome-wide expression profiling in head and neck squamous cell carcinoma (HNSCC) for regions of the tumor, the margin of surgical resecate (MSR) and normal mucosa (NM), we here proceed with respective analysis of cases after stratification according to the expression status of tenascin (Ten). Materials and Methods: Tissue specimens of each anatomical site were analyzed by immunofluorescent detection of Ten, fibronectin (Fn) and galectin-1 (Gal-1) as well as by microarrays. Results: Histopathological examination demonstrated that Ten⁺Fn⁺Gal-1⁺ co-expression occurs more frequently in samples of HNSCC (55%) than in NM (9%; p<0.01). Contrary, the Ten⁻Fn⁺Gal-1⁻ (45%) and Ten⁻Fn⁻Gal-1⁻ (39%) status occurred with significantly (p<0.01) higher frequency than in HNSCC (3% and 4%, respectively). In MSRs, different immunophenotypes were distributed rather equally (Ten⁺Fn⁺Gal-1⁺=24%; Ten⁻Fn⁺Gal-1⁻=36%; Ten⁻Fn⁻Gal-1⁻=33%), differing to the results in tumors (p<0.05). Absence/presence of Ten was used for stratification of patients into cohorts without a difference in prognosis, to comparatively examine gene-activity signatures. Microarray analysis revealed i) expression of several tumor progression-associated genes in Ten⁺ HNSCC tumors and ii) a strong up-regulation of gene expression assigned to lipid metabolism in MSRs of Ten⁻ tumors, while NM profiles remained similar. Conclusion: The presented data reveal marked and specific changes in tumors and MSR specimens of HNSCC without a separation based on prognosis.