Aberrant Genetic Changes in Lung Cancer : p16^<INK4a> and p14^<ARF>

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The CDKN2 gene on the short arm of chromosome 9p encodes two different cell cycle regulatory proteins, p16^<INK4a> and ARF. P16^<INK4a> and p14^<ARF> play an important role in independent cell cycle regulatory pathways, the retinoblastoma pathway and the p53 pathway, respectively. We have examined the expression of p16^<INK4a> and p14^<ARF> using competitive RT-PCR in 60 NSCLCs and matching normal lung tissues. The intensities of bands for p16^<INK4a> and p14^<ARF> were nearly equal or the intensity of p16^<INK4a> band slightly exceeded that of p14^<ARF> in the normal lung tissues (n=60). In 38 tumors the intensity of p16^<INK4a> band was similar to or slightly weaker than that of p14^<ARF>. In 6 tumors the intensity of p16^<INK4a> band was weaker than that of p14^<ARF>. In 15 tumors the intensity of p14^<ARP> band was very strong and p16^<INK4a> band was barely visible. In only one tumor the intensity of p16^<INK4a> band was very strong, while the band of p14^<ARF> was barely visible. The ratio of the intensity of p16^<INK4a> to p14^<ARF> band had an interesting correlation with the tumor's clinicopathological characteristics. The p stage II-IV tumors had significantly lower p16^<INK4a> to p14^<ARF> ratios than the p stage I tumors (p=0.036). The T2-4 tumors had significantly lower p16^<INK4a> to p14^<ARF> ratios than the T1 tumors (p=0.005). The N1-3 tumors had significantly lower p16^<INK4a> to p14^<ARF> ratios than the N0 tumors (p=0.014). Our results suggest that the ratio of expression of p16^<INK4a> to p14^<ARF> tends to decrease during the progression of NSCLC.