Loss of p16INK4A Expression and HomozygousCDKN2ADeletion Are Associated with Worse Outcome and Younger Age in Thymic Carcinomas

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Abstract

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.

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