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The Prognostic Value of Thymidylate Synthase and p53 Expression in Patients Treated with Induction Chemotherapy for Squamous Cell Carcinoma of the Head and Neck

^a The Human Monoclonal Antibody Laboratory; ^b The Division of Otolaryngology, Beth Israel Deaconess Medical Center; ^c The Head and Neck Oncology Program; ^d The Division of Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; ^e The Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts, USA; ^f the Department of Oncology, The Queen's University of Belfast, Belfast, United Kingdom

Correspondence: Marshall R. Posner, M.D., Head and Neck Oncology Program, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA. Telephone: 617-632-3090; Fax: 617-632-4448; e-mail: marshall_posner{at}dfci.harvard.edu

Thymidylate synthase (TS) and p53 are central molecules in the regulation of cell growth. Differences in the intracellular expression of these proteins by tumor cells may have predictive value for response to chemotherapy and early failure in patients with squamous cell cancer of the head and neck (SCCHN). Immunohistochemistry was used to assess the tumor cell expression of TS and p53 in pre-therapy biopsies from patients with advanced SCCHN treated with an induction chemotherapy protocol, PFL. Samples were available from 11 of 16 nonresponders, 13 of 19 early failures with progression within 24 months of treatment, and a random selection of 13 from 45 long-term, disease-free survivors (LTS). High TS expression was seen in the majority of samples from all three groups, 67% versus 78% versus 93%, respectively; however, only one of seven (14%) samples with low TS was from a LTS patient. TS expression did not differ in patients by sex, age, site of primary tumor, differentiation or stage. p53 was expressed in 33% of patient samples and did not predict response or correlate with sex, age, site of primary tumor, differentiation, or stage. Small primary tumors with extensive nodal disease were less likely to express p53 than larger primary tumors with or without nodal involvement. The data suggest that TS and p53 content have a limited prognostic value in patients treated with PFL, although tumors with lower TS expression appeared to be less likely to respond. Differences between this study and other investigations of TS and p53 may be disease site- and regimen-specific. Statistically significant differences between response groups may emerge from larger, site-specific, protocol-driven studies of TS and p53.

Key Words. Cisplatin • 5-Fluorouracil • Immunohistochemistry