Interleukin 4, interleukin 6 and osteopontin-serological markers of head and neck malignancy in primary diagnostics: A pilot study

The progression of head and neck squamous cell carcinoma (HNSCC) is stimulated by various angiogenic peptides and growth factors. A correlation between tumor progression and the secretion of various serological mediators in patients with malignant tumors of the head and neck is of major interest for tumor diagnostics, evaluation of the therapy response and it may predict prognosis by specifying the individual tumor biology. Established chemotherapeutic regimes for head and neck tumors usually consist of platinum-based chemotherapeutic drugs and 5-fluorouracil (5-FU). The present pilot study sought to assess the eligibility of seven serological factors as biomarkers for malignant tumors of the head and neck: Platelet-derived growth factor, vascular endothelial growth factor, epidermal growth factor receptor, osteopontin, granulocyte-colony stimulating factor, interleukin-4 (IL-4) and IL-6. The serum levels of each factor in 20 patients receiving concomitant radiochemotherapy with cisplatin or carboplatin and 5-FU with curative intent were determined prior and subsequent to chemotherapy and were compared with 40 healthy controls. Another aim of the pilot study was to investigate whether the serum of patients showed significant differences in the concentrations of the analyzed factors at the start of concomitant radiochemotherapy compared with the controls, whether those markers indicated a neoplastic process and whether concomitant radiochemotherapy with cisplatin or carboplatin and 5-FU induced significant alterations of concentration compared with pre-therapeutic levels. The included patients were histopathologically diagnosed with HNSCC and the average age was 62.3 years. The serum samples of the patients were obtained during the course of regular pre- and post-chemotherapeutic blood draws one week prior to the start of radiochemotherapy and one week following the completion of chemotherapy. The healthy controls were collected from patients of the Sleep Laboratory of the Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital (Mannheim, Germany) without clinical evidence or laboratory signs of inflammation or history of a malignant disease. The average age was 50.3 years. The serological level of each factor was ascertained by enzyme-linked immunosorbent assay in duplicate. Serum levels of IL-4, IL-6 and osteopontin were significantly increased in patients with HNSCC compared with those in chemotherapy-naive healthy controls. IL-4 and osteopontin showed no significant therapy-associated alterations. Notably, IL-6 levels significantly increased post-therapeutically. Using logistic regression with osteopontin and IL-4, an individual risk-profile for random samples was calculated. IL-4, IL-6 and osteopontin appear to be suitable indicators of the neoplastic process as they are significantly increased in HNSCC patients compared with the control group. With the exception of IL-6, whose levels were in fact increased following therapy, a significant therapy-associated alteration of these factors was missing. Therefore, these serological markers failed to predict the therapy response, but they may be valuable as a screening instrument in primary diagnostics.