Biochemical and molecular markers | 109
on about a possible predictive role. Because the proportion of rectal tumors carrying a BRAF mutation is very low, BRAF does not seem to be a very important biomarker in rectal cancer. KRAS status also has been shown to be of prognostic value. In about 40% of all rectal tumors KRAS is mutated. KRAS mutant tumors have a poor prognosis and a higher chance of recurrence. In the QUASAR trial this difference was even more pronounced for tumors located in the rectum as compared to tumors in other parts of the colon. In this trial the reduced risk of recurrence with chemotherapy was comparable between KRAS wild type and KRAS mutated tumors. However, for the prediction of response to EGFR-inhibitors, KRAS status has a predictive value. This has been confirmed for metastatic colorectal cancer in a recent meta-analysis [28].
Conclusion and perspective of biomarkers for treatment decisisons Biochemical and molecular biological factors could help in treatment decision making along the different treatment steps in the treatment of rectal cancer. This would allow more tailored treatment approaches thereby improving quality of life with even the benefit of more effective treatments. When analyzing the current value of these biomarkers in treatment decision-making, it is important to identify markers as being prognostic or predictive or even both. In rectal cancer, the only markers reaching clinical relevance in prognosis so far are deficient MMR, Kras and Braf, however its frequency in rectal cancer is rather low with only 1-4 % deficient MMR, 30-35% Kras mutation and 2-3 % Braf mutation [25]. The defective MMR genes hMLH-1, hMSH-2, PMS-2 and hMSH-6, detected by immunohistochemistry or by microsatellite testing showed a prognostic value in a meta-analysis [29], in the PETACC trial [30], the QUASAR and numerous single centre studies, which might lead to MMR related treatment decisions in the near future. Kras status has also been shown to be of prognostic value. Kras mutant tumors have a worse prognosis and a higher chance of recurrence. For EGFR-inhibitor therapy, the Kras status even reaches a predictive value.