Aberrant cytokine expression in serum of patients with adenoid cystic carcinoma and squamous cell carcinoma of the head and neck.

BACKGROUND: Squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) represent 2 clinically important subtypes of head and neck cancer. Our objective was to characterize and compare cytokine profiles in the systemic circulation of patients with SCC and ACC. METHODS: Multiplex analysis of 10 different cytokines (interleukin [IL]-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon [IFN]-gamma, and tumor necrosis factor [TNF]-alpha) in the serum of patients with SCC (n = 20) and ACC (n = 20) and healthy controls (n = 20) was performed using the Luminex fluorescent-bead technology. RESULTS: Patients with SCC as well as patients with ACC showed an altered cytokine profile compared with healthy individuals. In patients with SCC, significantly elevated serum levels of the proinflammatory cytokines, IL-6 and IL-8, were observed. In patients with ACC, IL-8 serum levels were significantly elevated, and IL-6 serum levels were only increased in a subset of patients. CONCLUSIONS: A similar serum cytokine profile, with the predominance of proinflammatory cytokines, was observed in patients with SCC and ACC. The newly defined cytokine profile in ACC patients may form the basis for future investigations to explore the role of cytokines in ACC tumor progression and their potential value as predictive biomarkers.

Comprehensive analysis of the p53 status in mucosal and cutaneous melanomas.

The abrogation of the function of the "gatekeeper of the genome", p53, is the most prevalent molecular alteration in solid human tumors. Regarding melanomas the involvement of p53 alterations is discussed controversially to date. In order to evaluate the status of p53 in detail, primary tumors and metastases of 63 sporadic cutaneous (CM) and mucosal (MuM) melanomas were examined by immunohistochemistry and sequence analysis of the entire coding region of the p53 transcript, i.e., exons 2 to 11. In addition, loss of heterozygosity (LOH) and loss of allele-specific transcription (LOT) were determined. Accumulation of the p53 protein occurred in most of the CM and MuM specimens (71% and 58%, respectively). In contrast, protein stabilizing p53 mutations were observed in 14% of the CM and no mutation was found in MuM specimens. Two of the aberrations located outside the core domain. LOH was detected in 22% CM and 58% MuM, and LOT in 25% of the CM specimens. The genotype distribution at the polymorphic p53 codon 72 in melanoma patients differed significantly from control subjects. The calculation of odds ratios (OR) and 95% confidence intervals (CI) indicated an increased risk for developing cutaneous melanomas in individuals carrying the Pro-coding allele. Altogether, aberrant p53 expression appears to be a common event in both CM and MuM.

p53, p63 and p73 expression in squamous cell carcinomas of the head and neck and their response to cisplatin exposure.

p63 and p73 share significant structural and functional homologies with the tumour suppressor p53. Unlike the p53 gene, both encode for several isoforms which vary in their NH2 and COOH termini with variable and, in part, opposed biological functions. The objective of the present study was to analyse the expression profiles of p53 family members in squamous cell carcinomas of the head and neck (HNSCC) and their alterations caused by exposure to the clinically active drug cisplatin. Using multiplex RT-PCR combined with the Southern technique, we determined transcription of p53 family members in 10 established HNSCC cell lines. In the majority of HNSCC, p53 and different p63/p73 isoforms were expressed with cell-line-specific patterns for composition and intensity of transcript expression. Exposure to cisplatin caused multiple alterations in the p63 and p73 profiles suggesting a complex regulation which may influence the sensitivity to chemotherapy.