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. 2006 Dec 18;95(12):1670-7.
doi: 10.1038/sj.bjc.6603479. Epub 2006 Nov 21.

The status of CDKN2A alpha (p16INK4A) and beta (p14ARF) transcripts in thyroid tumour progression

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The status of CDKN2A alpha (p16INK4A) and beta (p14ARF) transcripts in thyroid tumour progression

A Ferru et al. Br J Cancer. .

Abstract

CDKN2A locus on chromosome 9p21 encodes two tumour suppressor proteins pl6INK4A, which is a regulator of the retinoblastoma (RB) protein, and p14ARF, 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 p14ARF and pl6INK4A 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 pl6INK4a (P=0.006) in follicular adenomas and close to statistical significance for p14ARF 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 p14ARF 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.

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Figures

Figure 1
Figure 1
Box plot diagrams showing the expression levels of p14ARF, p16INK4A and E2F1. After normalization of sample to their own GAPDH level, data are expressed in 22−ΔCt*1000. OA: oncocytic adenomas; FA: follicular adenomas; FC: follicular carcinomas; PC: papillary carcinomas.
Figure 2
Figure 2
Immunohistochemical detection for p14ARF and p16INK4A. (A) Follicular adenoma, case 1: Increased p14ARF and p16INK4A expression in tumour (T) when compared to nontumoral tissue (N). (B) Papillary carcinoma, case 30: increased nuclear p14ARF expression in tumor (T30) when compared to nontumoral tissue (N30). Case 23: cytoplasmic delocalisation of p14ARF in tumour (T23), when compared to nontumoral (N23). N: nontumoral adjacent tissue, T: Tumour.

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