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Intermediate filaments are involved in cell migration and intracellular signal transduction pathways. In a variety of organs, the expression of distinct intermediary filaments are further associated with distinct steps of malignant transformation. In this study, we seeked to define the cytokeratin (Ck) expression pattern in oral leukoplakia and oral squamous cell carcinoma (OSCC). One hundred and ninety-two patients with OSCC, 117 patients with oral leukoplakia without dysplasia (OL) and 23 with oral leukoplakia with dysplasia (squamous intraepithelial neoplasia) (OLD) of the oral cavity were investigated for the immunohistochemical expression of Ck 5-6, Ck 8/18, Ck 1 Ck 10, Ck 14, Ck 19 using the tissue microarray technique. Correlations between clinical features and the expression of cytokeratins were evaluated statistically by chi2 tests. The expression of Ck 8/18, Ck 19 and Ck 1 was seen in 3.1% (Ck 8/18), 12.5% (Ck 19), 75.4% (Ck 1) of all leukoplakias, 1.0% (Ck 8/18), 9.4% (Ck 19), 76.8% (Ck 1) in OL, 13.0% (Ck 8/18), 27.3% (Ck 19), 68.4% (Ck 1) in OLD and was significantly associated with the degree of dysplasia (Ck 8/18 p<0.01; Ck 19 p<0.01; Ck 1 p<0.01) and the acquisition of invasive growth properties. The highest frequencies were observed in invasive squamous cell carcinomas. The expression of Ck 8/18 and Ck 19 in transformed oral lesions can be regarded as an early feature in the pathogenesis of invasive OSCC. However, the aberrant expression of Ck 8/18 and Ck 19 in an even higher frequency in invasive carcinomas characterizes the expression of typical glandular cytokeratins as a general progression marker in squamous cell carcinomas. These results can be interpreted as first hints that oral leukoplakias with an expression of Ck 8/18 or 19 independent of dysplasia, should be resected totally since they might indicate an increased progression potential.

Cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDKIs), such as p21 and p27, exert a direct control on the cell cycle. p21 and p27 are negative regulators of cyclin-dependent kinases and in this function they are negative check-point regulators of the cell cycle. We therefore aimed to evaluate p21 and p27 expression in oral squamous cell carcinomas (OSSC) to determine the value as a prognostic marker. One hundred and ninety-two patients with histologically proven, surgically treated squamous cell carcinoma of the oral cavity were eligible for the study and investigated for the expression of p21 and p27 by means of tissue microarrays (TMAs). Immunohistochemical screening under identical condition were carried out with antibodies against p21 and p27. Correlations between clinical features and the expression of the respective antibodies were evaluated statistically by Kaplan-Meier curves, log-rank and chi(2) tests. The expression of p21 correlated significantly with an increased prognosis in the log-rang test (p=0.01). No significant correlation was found between the expression of p27 and the overall survival rate. In multivariate Cox analysis, p27 was indicated as independent predictor of survival prognosis in the subgroup of nodal positive carcinomas, p27 positive tumours showed a significantly better survival prognosis (p=0.03). p21 and p27 in carcinoma of oral cavity seem to be predictive parameter in regulation and prognosis of squamous cell carcinomas. A p21 negative subgroup of OSCC may benefit from additional radio or radiochemotherapy.

Besides its immunoregulatory effects, interleukin-4 (IL-4) has growth inhibitory activity on cells from human solid tumors, and IL-4 receptors are present on tumor cells including cells from head and neck squamous cell carcinomas. We have conducted a phase I/II trial in patients with oral squamous cell carcinomas of T(4), N(+) (1 exception) stage to assess safety and therapeutic activity of recombinant human (rh) IL-4 applying the drug intratumorally 3 times a week with dose escalation for a duration of 4 weeks. A total of 7 patients entered the study using doses of 1, 3, and 5 microg/kg. There was no reduction of tumor size with 1 patient showing clear progression of the tumor after 4 weeks of treatment. This, and the observation of limiting toxicity occurring as local pain at the injection site, led to study termination. Therefore, rhIL-4 cannot be recommended as an antitumor drug in this disease using monotherapy with the schedules applied in this trial.