Prognostic significance of cell-cycle regulatory proteins for outcome after primary radiochemotherapy in patients with advanced head and neck cancer

Background: Primary radiochemotherapy is gaining increasing importance for the treatment of advanced head and neck squamous cell carcinomas. However, there is a lack of clinical factors concerning prognostic information in re lation to treatment. In this pilot study, we examined whether molecular fac tors can provide such information. Patients and methods:The expression patt erns and their possible prognostic relevance of the cell cycle regulatory p roteins p53, p21(WAF/CIP1), Rb, p16(INK4A), CDK4 and Cyclin D1, MIB1 (Ki-67 ) and BCL-2 were analysed in pretreatment: tumor biopsies from 43 patients with advanced carcinomas of the oropharynx (n=26), hypopharynx (n=10) and l arynx (n=7) by applying immunohistochemistry to paraffin sections of tumor specimens. All patients were treated by the same method of an accelerated " concomitant boost" radiochemotherapy with carboplatin in a phase II study. Median followup lime was 56 months. Results: No correlation was found betwe en any of the markers and the remission rate, T-stage, N-stage, rate of loc o-regional recurrences and distant metastases. However, independent of the tumor stage, patients with CDK4/cyclin-D1 overexpressing tumors had a signi ficantly shortened overall survival (P=0.014 and 0.026, respectively). Conc lusion: The results of this pilot study indicate that CDK4 and cyclin D1 ov er-expression provide useful prognostic information about clinical outcome after primary radiochemotherapy of head and neck cancer patients.