p16 gene alterations in locally advanced squamous cell carcinoma of the head and neck.

We previously documented the presence of mutations/deletions in the tumor suppressor gene p16 in squamous cell carcinoma of the head and neck (SCCHN). However, the association of these p16 alterations with clinical outcome is unknown. In this study, RNA was isolated from 19 frozen SCCHN from 19 patients who were previously enrolled in the OSU intensification regimen 2. Quantitative real-time RT-PCR and direct sequencing analysis was then performed on the specimens to detect p16 gene alterations. Clinical outcome for each patient was updated and correlated with the p16 alterations found. Five tumor specimens were found to have no or very low expression of p16 when compared with normal tissue. The remaining 14 tumor samples demonstrated overexpression of p16 relative to the level of expression in normal tissue. Sequence analysis of the p16 RT-PCR product from these specimens allowed identification of mutational changes in the coding sequence of p16 in four of the SCCHN specimens. Subsequent analysis of clinical outcome associated with locoregional/distant failure demonstrated no correlation with either altered expression of p16 or mutational status of p16. Results from this study indicate that p16 alterations are frequently found in this cohort of SCCHN. However, p16 alterations alone do not appear to be associated with clinical outcome.

Expression of the serine protease DESC1 correlates directly with normal keratinocyte differentiation and inversely with head and neck squamous cell carcinoma progression.

BACKGROUND: As part of ongoing studies aimed at identifying the molecular events involved in head and neck squamous cell carcinoma progression, we recently isolated a novel serine protease, DESC1. This study was conducted to further characterize DESC1. METHODS: Specimens of normal, dysplastic, and carcinomatous oropharyngeal mucosa (n = 31) were evaluated for DESC1 immunoreactivity using standard streptavidin-biotin immunoperoxidase techniques. Between-lesion stain intensity values were analyzed using multiple Wilcoxon tests. DESC1 expression was also evaluated in cultured human keratinocytes after induction of differentiation by calcium challenge, with subsequent real-time reverse transcriptase-polymerase chain reaction quantification. RESULTS: DESC1 immunoreactivity decreased as lesions approached a malignant phenotype. Post hoc testing comparing the different lesion types and DESC1 staining values showed significance between "normal" and "carcinoma" (p = .0017) groups. Induction of normal keratinocyte differentiation by calcium challenge was accompanied by an increase in DESC1 expression (p = .002). CONCLUSIONS: These results suggest downregulation of DESC1 during squamous cell carcinoma progression and upregulation during normal epithelial differentiation.