P14ARF Is Down-regulated During Tumour Progression and Predicts the Clinical Outcome in Human Breast Cancer

The objective of this study was to determine the mRNA expression for p14 and p16 in a cohort of women with breast cancer. Materials and Methods: Breast cancer specimens (N= 127) and normal tissue (N=23) specimens were studied. Transcript levels were determined using quantitative polymerase chain reaction (PCR), and were correlated with clinicopathological data collected over 10 years. Results: Higher p14 mRNA transcript levels were associated with non-cancerous background tissue specimens (median copy numbers: 103 vs. 4, p=0.0095), with better overall and disease-free survival, and in TNM2 stage tumours (TNM2 vs. TNM1, 27.2 vs. 3.5, p=0.049; TNM1/TNM2 vs. TNM3/4, 26 vs. 2, p=0.009). There was no significant relationship between p16 levels and clinicopathological parameters. A correlation between p14 and human telomerase reverse transcriptase (hTERT) levels was observed (r=0.406, p=0.00005). Conclusion: p14 expression seems to increase initially in early breast cancer and decrease with further tumour progression. p14 may be induced to counteract immortalisation and hTERT surge.