Pricolo V E, Finkelstein S D, Wu T T, Keller G, Bakker A, Swalsky P A, Bland K I
Department of Surgery, Brown University School of Medicine, Providence, Rhode Island, USA.
Am J Surg. 1996 Jan;171(1):41-6. doi: 10.1016/S0002-9610(99)80071-3.
Genetic mutations involving oncogenes and tumor-suppressor genes occur in carcinogenesis, and may affect biologic behavior of neoplasms. In this study, we analyzed the prognostic value of mutational analysis in colon carcinoma.
Archival pathology specimens from 70 consecutive patients, resected for stage III colon carcinoma, were analyzed for point mutations by amplification and direct sequencing of exons from the K-ras-2 and the TP53 genes (topographic genotyping). Mutations were compared with adverse histopathologic features (poor differentiation, vascular and lymphatic invasion, mucin production) as prognostic markers.
Five-year survival was 75% in patients with nonmutated lesions, significantly lower (21%) with TP53 mutations (P = 0.01), and intermediate with K-ras-2 only (45%) or both K-ras-2 and TP53 mutations (36%). A TP53 mutation carried the highest relative risk of death (2.39; 95% confidence interval, 1.29 to 4.42; P = 0.006). There was an additive effect on the risk of death between TP53 mutations and adverse histopathologic features.
The information derived from mutational analysis is creating new prognostic variables that may play a role in the choice of therapy for colorectal carcinoma.
致癌过程中会发生涉及癌基因和肿瘤抑制基因的基因突变，且这些突变可能影响肿瘤的生物学行为。在本研究中，我们分析了结肠癌突变分析的预后价值。
对70例连续接受III期结肠癌切除术患者的存档病理标本进行分析，通过对K-ras-2和TP53基因外显子进行扩增和直接测序来检测点突变（地形基因分型）。将突变与不良组织病理学特征（低分化、血管和淋巴管浸润、黏液产生）作为预后标志物进行比较。
未发生突变的患者5年生存率为75%，TP53基因突变的患者生存率显著降低（21%）（P = 0.01），仅K-ras-2基因突变的患者生存率处于中间水平（45%），K-ras-2和TP53基因均发生突变的患者生存率为36%。TP53基因突变患者的死亡相对风险最高（2.39；95%置信区间为1.29至4.42；P = 0.006）。TP53基因突变与不良组织病理学特征之间对死亡风险存在相加效应。
从突变分析中获得的信息正在产生新的预后变量，这些变量可能在结直肠癌治疗方案的选择中发挥作用。
