p16INK4A and p14ARF gene promoter hypermethylation as prognostic biomarker in oral and oropharyngeal squamous cell carcinoma: a review.

Head and neck squamous cell carcinoma is a heterogeneous group of tumors with each subtype having a distinct histopathological and molecular profile. Most tumors share, to some extent, the same multistep carcinogenic pathways, which include a wide variety of genetic and epigenetic changes. Epigenetic alterations represent all changes in gene expression patterns that do not alter the actual DNA sequence. Recently, it has become clear that silencing of cancer related genes is not exclusively a result of genetic changes such as mutations or deletions, but it can also be regulated on epigenetic level, mostly by means of gene promoter hypermethylation. Results from recent studies have demonstrated that DNA methylation patterns contain tumor-type-specific signatures, which could serve as biomarkers for clinical outcome in the near future. The topic of this review discusses gene promoter hypermethylation in oral and oropharyngeal squamous cell carcinoma (OSCC). The main objective is to analyse the available data on gene promoter hypermethylation of the cell cycle regulatory proteins p16(INK4A) and p14(ARF) and to investigate their clinical significance as novel biomarkers in OSCC. Hypermethylation of both genes seems to possess predictive properties for several clinicopathological outcomes. We conclude that the methylation status of p16(INK4A) is definitely a promising candidate biomarker for predicting clinical outcome of OSCC, especially for recurrence-free survival.

Importance of tumor volume in supraglottic and glottic laryngeal carcinoma.

PURPOSE: The aim of our study was to assess the prognostic value of tumor volume compared to and in addition to T-stage on local control (LC), disease-free survival (DFS), and overall survival (OS) in glottic and supraglottic laryngeal carcinoma patients. PATIENTS AND METHODS: In 150 patients, we determined tumor volume on diagnostic CT scans. We applied crude and multivariable Cox regression analysis to relate volume (continuous), T-stage and the combination to 5-year DFS, OS, and LC. Before, we examined the linearity assumption of the association between volume and outcome with restricted cubic spline functions. Prognostic performance of the models was examined by determination of the model's discrimination. Discriminative ability was determined with the C statistic referring to the ability to discriminate between patients who do and do not develop an event during follow-up. RESULTS: A strong association between tumor volume and DFS and OS was found. The restricted cubic spline plot did not indicate a non-linear relationship between tumor volume and DFS and local control. Tumor volume demonstrated a better discriminative ability to predict DFS and OS compared to T-stage (0.68 and 0.57 vs. 0.59 and 0.54, respectively). For local control, T-stage showed a higher discriminative ability than tumor volume (0.63 vs. 0.61). The combined model increased discriminative power (0.69). CONCLUSION: Volume seems to be more important than T-stage in prediction of DFS or OS in laryngeal squamous cell carcinoma patients. Perhaps prediction of DFS, OS, and LC could be improved by including tumor volume into the staging process.

[Five patients with metastasized basal-cell carcinoma]. / Vijf patiënten met een gemetastaseerd basaalcelcarcinoom.

During the period 1986-2001, a metastasised basal-cell carcinoma of the head was diagnosed in five patients (a 35-year-old woman and four men aged 40, 44, 54 and 54 years) at the Utrecht University Medical Centre, the Netherlands. Metastases were found in the cervical lymph nodes, the skeleton, the parotid region and the lungs. The tumours were all of the morphoeic or 'wispy' type. The treatment consisted of excision and sometimes radiotherapy. Two patients died, one of whom of a cause unrelated to the tumour, two patients were free of symptoms 24 months after the last treatment and one patient was still being treated with radiotherapy. It is often assumed that basal-cell carcinomas do not metastasised, but a frequency of 0.0028-0.55% is reported in the literature. An important risk factor is the size of the tumour. Surgical excision or Mohs' micrographic surgery is the preferred method of treatment because this allows histological inspection of the excised margins. Due to the low incidence, there are no clear therapeutic guidelines for the treatment of patients with metastasised basal-cell carcinoma.