The status of CDKN2A alpha (p16(INK4A)) and beta (p14(ARF)) transcripts in thyroid tumour progression

CDKN2A locus on chromosome 9p21 encodes two tumour suppressor proteins pl6(INK4A), which is a regulator of the retinoblastoma (RB) protein, and p14(ARF), which is involved in the ARF–Mdm2–p53 pathway. The aim of this study was to determine if CDKN2A gene products are implicated in differentiated thyroid carcinogenesis and progression. We used real-time quantitative RT–PCR and immunohistochemistry to assess both transcripts and proteins levels in 60 tumours specimens. Overexpression of p14(ARF) and pl6(INK4A) was observed in follicular adenomas, follicular carcinomas and papillary carcinomas, while downregulation was found in oncocytic adenomas compared to nontumoral paired thyroid tissues. These deregulations were statistically significant for pl6(INK4a) (P=0.006) in follicular adenomas and close to statistical significance for p14(ARF) in follicular adenomas (P=0.06) and in papillary carcinomas (P=0.05). In all histological types, except papillary carcinomas, we observed a statistically significant relationship between p14(ARF) and E2F1 (r=0.64 to 1, P<0.05). Our data are consistent with involvement of CDKN2A transcript upregulation in thyroid follicular tumorigenesis as an early event. However, these deregulations do not appear to be correlated to the clinical outcome and they could not be used as potential prognostic markers.