Loss of p16INK4A Expression and Homozygous CDKN2A Deletion Are Associated with Worse Outcome and Younger Age in Thymic Carcinomas.

INTRODUCTION

Thymic carcinomas are aggressive tumors. Biomarkers and alternative treatment modalities are needed. We studied the expression of p16 and cytogenetic abnormalities of cyclin-dependent kinase inhibitor 2A gene (CDKN2A) and correlated findings with clinical features and outcome in a large cohort of thymic carcinomas.

METHODS

Thymic carcinomas (1963-2013) were stained with p16. Fluorescence in situ hybridization was utilized to assess for the presence of CDKN2A gene (at 9p21). Statistical analysis was performed.

RESULTS

A total of 27 patients (including 15 men) with thymic carcinoma at a median age of 51.7 years at time of surgery and available follow-up information were included. Loss of p16 expression was found in 12 of 26 cases (46.2%) and was associated with worse recurrence and metastasis-free survival (p = 0.01), which in multivariate analysis was independent of resection status (p = 0.007) and T stage (p = 0.01). Four of 22 tumors (18.2%) showed homozygous CDKN2A deletion that was correlated with loss of p16 expression (p=0.02). In tumors of the squamous cell carcinoma subtype, loss of p16 expression was associated with worse recurrence and metastasis-free survival (p = 0.006) and overall survival (p = 0.0009). Patients with thymic squamous cell carcinomas lacking p16 expression were younger (p = 0.006). Although similar trends for younger age were noted in patients with thymic squamous cell carcinomas with homozygous CDKN2A deletion, the small number of such cases (n = 2) did not allow for statistical analysis.

CONCLUSIONS

Loss of p16 expression and homozygous deletion of CDKN2A are promising prognostic biomarkers in thymic carcinoma. On the basis of our findings, a subset of thymic carcinomas have the potential to respond to CDK4/6 inhibitors; however, further functional studies are needed.