p14 super(ARF) Protein Expression Is a Predictor of Both Relapse and Survival in Squamous Cell Carcinoma of the Anterior Tongue

PURPOSE: The INK4A-ARF locus at chromosome 9p21 is frequently altered in head and neck squamous cell carcinoma (SCC) and encodes two distinct tumor suppressors, p16 super(INK4A) and p14 super(ARF). This study addressed the role of p14 super(ARF) as a potential prognostic marker in this disease. Expe...

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Published in:Clinical cancer research 2005-06, Vol.11 (11), p.4107-4116
Main Authors: Kwong, Rhonda A, Kalish, Larry H, Nguyen, Tuan V, Kench, James G, Bova, Ronaldo J, Cole, Ian E, Musgrove, Elizabeth A, Sutherland, Robert L
Format: Article
Language:English
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Summary:PURPOSE: The INK4A-ARF locus at chromosome 9p21 is frequently altered in head and neck squamous cell carcinoma (SCC) and encodes two distinct tumor suppressors, p16 super(INK4A) and p14 super(ARF). This study addressed the role of p14 super(ARF) as a potential prognostic marker in this disease. Experimental Design: p14 super(ARF) protein expression was assessed by immunohistochemistry in a cohort of 140 patients with SCC of the anterior tongue. Using univariate and multivariate Cox's proportional hazards models, the outcomes examined were time to disease recurrence or death, with or without clinicopathologic covariates, including nodal status, disease stage, treatment status, Ki-67 staining, and molecular markers with known functional or genetic relationships with p14 super(ARF) (p16 super(INK4A), p53, pRb, p21 super(WAF1/CIP1), E2F-1). RESULTS: On multivariate analysis, p14 super(ARF) positivity (nucleolar p14 super(ARF) staining and/or nuclear p14 super(ARF) staining in greater than or equal to 30% of tumor cells) was an independent predictor of improved disease-free survival (DFS; P = 0.002) and overall survival (OS; P = 0.002). This was further enhanced when p14 super(ARF) positivity was cosegregated with positive ( greater than or equal to 1%) p16 super(INK4A) staining (DFS, P < 0.001; OS, P < 0.001). Patients whose cancers were p14 super(ARF) negative and p53 positive (>50%) had the poorest outcome (DFS, P < 0.001; OS, P < 0.001) of any patient subgroup analyzed. CONCLUSIONS: These data show that in patients with SCC of the tongue, combined nuclear and nucleolar expression of p14 super(ARF) protein predicts for improved DFS and OS independent of established prognostic markers.
ISSN:1078-0432