Bleeker W A, Hayes V M, Karrenbeld A, Hofstra R M, Verlind E, Hermans J, Poppema S, Buys C H, Plukker J T
Department of Surgery/Surgical Oncology, University Hospital Groningen, The Netherlands.
Dis Colon Rectum. 2001 Mar;44(3):358-63. doi: 10.1007/BF02234733.
Mutations in K-ras and TP53 genes are common in colorectal cancer. They affect biologic behavior and might influence chemotherapy susceptibility in these tumors. We investigated whether the survival of patients with Dukes C colon cancer treated with adjuvant chemotherapy is influenced by K-ras and TP53 mutations.
Mutation screening of the hot spots of the K-ras gene and of the evolutionarily conserved regions of the TP53 gene was performed by denaturing gradient gel electrophoresis technique in formalin-fixed paraffin-embedded specimens of 55 consecutive patients with Dukes C colon cancer treated with adjuvant 5-fluorouracil-based chemotherapy. The median follow-up was 47 (range, 32-66) months.
Alterations in the mutation hot spots of K-ras were found at codon 12 (n = 11) and 13 (n = 4) in 15 of the 55 carcinomas (27 percent). No mutation was found at codon 61. Mutations of a probably causative nature in the evolutionarily conserved regions (exons 5-8) of the TP53 gene were found in 24 tumors (44 percent). K-ras and TP53 mutations were found equally in the group with recurrent disease (7/26 (26 percent) and 12/27 (44 percent), respectively) and in the group without recurrences (8/28 (24 percent) and 12/28 (43 percent), respectively). Cancer-specific survival did not differ significantly between patients with K-ras or TP53 or both mutated and nonmutated tumors, respectively (log-rank test: K-ras, P = 0.72 and TP53, P = 0.77; K-ras and TP53, P = 0.8). Also, potentially aggressive K-ras codon 12 and 13 mutations had the same survival as tumors without these mutations (log-rank test; P = 0.73).
Patients with K-ras or TP53 or both mutated Dukes C colon tumors have the same survival as nonmutated tumors when treated with adjuvant chemotherapy. These data suggest that mutations in K-ras or TP53 alone are not prognostic indicators in patients with Dukes C colon cancer receiving adjuvant 5-Fluorouracil-based therapy.
K-ras和TP53基因的突变在结直肠癌中很常见。它们影响生物学行为，并可能影响这些肿瘤的化疗敏感性。我们研究了接受辅助化疗的Dukes C期结肠癌患者的生存是否受K-ras和TP53突变的影响。
采用变性梯度凝胶电泳技术，对55例接受以5-氟尿嘧啶为基础的辅助化疗的连续Dukes C期结肠癌患者的福尔马林固定石蜡包埋标本进行K-ras基因热点和TP53基因进化保守区域的突变筛查。中位随访时间为47（范围32 - 66）个月。
在55例癌中的15例（27%）中，发现K-ras突变热点在密码子12（n = 11）和13（n = 4）处发生改变。在密码子61处未发现突变。在24例肿瘤（44%）中发现TP53基因进化保守区域（外显子5 - 8）存在可能具有致病性质的突变。K-ras和TP53突变在复发组（分别为7/26（26%）和12/27（44%））和无复发组（分别为8/28（24%）和12/28（43%））中出现的比例相同。K-ras或TP53或两者均突变的肿瘤患者与未突变肿瘤患者的癌症特异性生存无显著差异（对数秩检验：K-ras，P = 0.72；TP53，P = 0.77；K-ras和TP53，P = 0.8）。同样，具有潜在侵袭性的K-ras密码子12和13突变的肿瘤与无这些突变的肿瘤生存情况相同（对数秩检验；P = 0.73）。
接受辅助化疗时，K-ras或TP53或两者均突变的Dukes C期结肠肿瘤患者与未突变肿瘤患者的生存情况相同。这些数据表明，单独的K-ras或TP53突变并非接受以5-氟尿嘧啶为基础的辅助治疗的Dukes C期结肠癌患者的预后指标。
