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Annals of Oncology 2006 17(Supplement 7):vii84-vii90; doi:10.1093/annonc/mdl958
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© 2006 European Society for Medical Oncology

symposium article

Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study

V. Bazan1,#, L. Bruno1,#, C. Augello1, V. Agnese1, V. Calò1, S. Corsale1, G. Gargano1, M. Terrasi1, V. Schirò1, G. Di Fede1, V. Adamo3, C. Intrivici1, A. Crosta1, G. Rinaldi1, F. Latteri2, G. Dardanoni6, N. Grassi2, M. R. Valerio1, G. Colucci4, M. Macaluso5 and A. Russo1,*

1 Section of Medical Oncology and 2 Section of Surgical Oncology, Department of Surgical and Oncology, Università di Palermo, Italy; 3 Unit of Medical Oncology, A.O. Universitaria Policlinico ‘G.Martino’, Università di Messina, Italy; 4 Division of Medical Oncology, National Institute of Oncology, Bari, Italy; 5 Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA; 6 Epidemiological Observatory Center of Sicilian Region, Palermo, Italy

* Correspondence to: Dr A. Russo, Section of Medical Oncology, Department of Oncology, Università di Palermo, Via del Vespro 127, 90127 Palermo, Italy. Tel: +39-091-6552500; Fax: +39-091-6554529; E-mail: lab-oncobiologia{at}usa.net

Background: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role.

Patients and methods: Ki-Ras, TP53 mutations and p16INK4A methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients.

Results: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16INK4A genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations

Conclusions: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques.

Key words: colorectal carcinoma, free-cell DNA, Ki-Ras, TP53


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