Ith other histological types (p = 0.0462). PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/20709720 Patients with fied the following independent prognostic factors affecting OS K-Ras gene mutations did not show a significant difference in time rates: primary tumor localization (HR 0.53; p = 0.0032); pre- to MC-207,110 dihydrochloride progression when treated with oxaliplatin chemotherapy, when treatment CEA level (HR 2.68; p < 0.0001); WHO performance compared with those with the wild-type K-Ras gene (Fig. 4). The status (HR 0.34; p = 0.0008); lymph node involvement grade significance of B-Raf gene status, WHO performance status, and Karnofsky performance status could not be assessed. (HR 1.94; p = 0.0107).Cancer Biology TherapyVolume 13 issuePredictive roles of K-Ras and B-Raf mutations on time to progression in CRC patients treated with oxaliplatin-based first-line palliative chemotherapy on the basis of multivariate analysis. These results are summarized in Table 4. Multivariate analysis identified resection of metastases (HR 0.43; p = 0.0249) and wild-type K-Ras gene (HR 0.49; p = 0.0451) as independent favorable predictive factors in patients with disseminated CRC who were treated with oxaliplatin-based first-line palliative chemotherapy regimens. However, no statistically significant effects of CEA levels and types of neoplasm could be seen. The significance of B-Raf gene status, WHO performance status, and Karnofsky performance status could not be assessed due to the small number of patients. Discussion Cancer treatment is increasingly based on targeted therapy, i.e., morphological identification of tumor histology, tumor staging and identification of target pathways and molecules. New insights into signaling processes gone astray in carcinogenesis broaden the scope of molecular diagnosis in cancer. Identification and validation of new prognostic and prognostic markers allow physicians to offer patient-targeted therapy from a broader range of options. Presently known biomarkers for CRC include the genetic instability status of the tumor, KRAS mutation status as a negative predictive marker for the overall rate of response to antiEGFR treatment in patients with metastatic cancer, and BRAF mutation as an unfavorable prognostic marker.18 The introduction of molecularly targeted drugs for the treatment of advanced CRC is based on emerging data on the molecular mechanisms responsible for its origin and development. Disturbances in the RAS/RAF/MEK/ERK signaling pathway are the most frequent and perhaps the most important observed defects, with activating mutations in the K-Ras and B-Raf genes playing key roles. The aims of this study were to evaluate the incidence of B-Raf and K-Ras gene mutation in patients with CRC regardless of disease stage, and to determine the prognostic significance of these mutations on time to progression in response to treatment with palliative chemotherapy. The role of select clinical and pathological variables as potential prognostic factors was also examined. Our analysis revealed K-Ras gene mutations in our patient population with an incidence of 32.6 with most K-Ras mutations located in codon 12 (27.8 ) compared with codon 13 (3.7 ), similar to previously reported data.8,19 We estimate the incidence of B-Raf gene mutations at 6.2 , occurring predominantly in exon 15. Further, our analysis shows that B-Raf mutations in exon 15 (V599E) account for nearly 90 of all mutations.Our study did not establish a prognostic role for B-Raf mutation status in CRC patients in contrast to the resul.