Specific c-K-ras gene mutations as a tumor-response marker in locally advanced rectal cancer treated with preoperative chemoradiotherapy

Background: Forty percent of patients with colorectal cancer develop mutati ons in the K-ras gene. Objective: Our objective was to evaluate whether the presence of c-K-ras ge ne mutations is a useful tumor-response marker in patients with locally adv anced rectal cancer treated with preoperative chemoradiotherapy. Material and Methods: Thirty seven patients with locally advanced rectal ca ncer were treated with preoperative chemoradiotherapy. Four to six weeks la ter, surgery was performed. Specimens were classified according to the UICC -AJC classification, ii segment of the tumor was obtained to analyze specif ic c-g-ras gene mutations. Restriction fragment length polymorphism (RFLP) and single strand confirmation polymorphism (SSCP) techniques were used wit h a set of probes to detect specific c-K-ras mutations in codons 12, 13, an d 61. The 37 patients were divided into Group A (with mutations) and Group B (without mutations). Results: All 37 patients completed the scheduled treatment. Group A consist ed of 12 patients, whose tumors were classified and specific c-K-ras mutati ons were located as follows: eight in codon 12, two in codon 13, and one in codon 61. Group B consisted of 25 patients. The tumors were classified and there were more early-stage tumors in Group A, whereas in Group B there we re more advanced-stage tumors (P = .05, respectively). The mean follow-up w as 36.2 +/- 18.3 months. All Group A patients survived, whereas 8 of the 25 patients in Group B died due to progressive metastatic disease. Survival i n Group A was 100%, whereas in Group B it was 59% (P = .03). Conclusions: The presence of specific c-g-ras mutations is an indicator of tumor response in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy and surgery. Therefore, responding patients may be more amenable to less radical surgical procedures based on c-K-ras mutations.