Cyclin D1 and FADD as Biomarkers in Head and Neck Squamous Cell Carcinoma

Abstract

Objective: Cyclin D1 and FADD (Fas-associated protein with death domain) regulate the cell cycle and apoptosis, respectively, and are located on chromosome 11q13.3, which is frequently amplified in head and neck squamous cell carcinoma (HNSCC). This study evaluates these proteins as predictors of clinical outcomes for HNSCC.

Method: Immunohistochemical assessment of 366 archival HNSCC specimens in tissue microarrays and correlation with retrospectively collected clinical data. Outcomes for patients with tumors that exhibited strong cyclin D1 or FADD staining were compared with outcomes for patients with weakly or non-staining tumors.

Results: Patients with tumors that were strongly positive for cyclin D1 had reduced overall (P = .010) and disease-free (P = .040) survival, while patients with tumors that were strongly positive for FADD had reduced overall (P = .019) and disease-specific (P = .049) survival. Together, the 2 markers effectively stratified overall (P = .002), disease-specific (P = .032), and disease-free (P = .059) survival. Strong cyclin D1 positivity correlated with higher overall stage (P = .023) and T-stage (P = .016), while strong FADD staining correlated with T-stage (P = .041). In multivariate analysis strong cyclin D1 staining was a better predictor of recurrence (P = .018) than strong FADD positivity, overall stage, and T-stage, and was independent of N-stage (P = .005).

Conclusion: Cyclin D1 and FADD may have utility as predictors of long-term outcomes for patients with HNSCC. Further study is needed to determine if these proteins predict response to different treatment approaches or assist in selecting patients for multi-modality therapy.