Colorectal cancer: biological factors as prognostic markers for a more targeted therapy
Faculty of Medicine and Health Sciences
Belgian journal of medical oncology. - Amsterdam, 2007, currens
, p. 168-172
University of Antwerp
Traditionally, TNM disease staging has been the main method of determining colorectalcancer (CRC) progress. However, its predictive value is limited since CRC should be regarded as a heterogeneous, multi-pathway disease. Validated prognostic, predictive, and toxicity markers are needed to achieve a more personal intervention, with the potential to increase efficacy and decrease toxicity. Currently, no molecular characteristics have emerged as consistent predictors of response to therapy. In this study, several biomarkers have been examined for their potential in determining the aggressiveness of the disease and the likelihood of tumour recurrence in a well-defined study population. Microsatellite instability (MSI) was proven not to be an independent prognostic factor in colon cancer. Consequently, conflicting data and incomplete understanding of the MSI-induced carcinogenesis mechanism, argues against using MSI as a single predictor of survival in CRC. Next, the presence of infiltrating lymphocytes in CRC was confirmed. Intra-epithelial infiltration of CD3+ and CD8+ T lymphocytes and stromal infiltration of CD3+ lymphocytes had a significant impact on the patients overall survival by univariate analysis, irrespective of MSI status. Subsequently, the presence of oncogenic high-risk human papillomavirus (HPV) in CRC was confirmed. As observed in head and neck carcinomas, the prevalence of HPV was significantly higher in younger patients. However, there was no significant difference in the distribution of the virus throughout the colon and no correlations were found between HPV and the other clinicopathological characteristics of survival. Finally, high-resolution melting analysis was found to be a sensitive in-tube method for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation detection, and KRAS mutation came up as a negative predictive factor for overall survival in patients with rectal cancer and for disease-free survival in stage II colon cancer patients. In conclusion, as yet no accepted molecular prognostic markers have been found in the clinical setting, although several biological factors show great potential to date. Largescale prospective randomized trials need to be carried out to determine the role of the various putative molecular markers.