The Prognostic Value of c-Kit, K-ras Codon 12, and p53 Codon 72 Mutations in Egyptian Patients With Stage II Colorectal Cancer
The Prognostic Value of c-Kit, K-ras Codon 12, and p53 Codon 72 Mutations in Egyptian Patients With Stage II Colorectal Cancer
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DOI：
10.1002/cncr.25417
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发表时间：
2010-11-01
期刊：
影响因子：
6.2
通讯作者：
Zekri, Abdel-Rahman N.
中科院分区：
文献类型：
--
作者：
El-Serafi, Mostafa M.;Bahnassy, Abeer A.;Zekri, Abdel-Rahman N.
背景：结直肠癌患者的预后主要取决于标准的临床病理因素。然而，具有相似疾病特征的患者表现出不同的结果，特别是在II期。因此，需要识别分子预后标志物来预测患者的结果。方法：应用免疫组织化学和分子生物学技术对90例II期大肠癌患者c-Kit(又称分化簇117[CD117]或KIT)、环氧合酶-2(COX-2)、肿瘤蛋白53(P53)和Kirsten鼠肉瘤病毒癌基因同源基因(K-ras)突变的预后价值进行评估。结果与标准临床病理预后因素、总生存期(OS)和无病生存期(DFS)相关。结果：COX2和c-Kit过表达分别占54.6%和59.3%。在47例患者中检测到P53过表达，其中29例有突变，并在第72、245和273密码子上检测到3个热点突变模式。在44例患者中检测到ras过表达，其中37例发生突变。多因素分析显示，c-Kit过度表达、P53密码子72突变、穿孔和功能状态是影响DFS的独立预后因素(P=0.054、P=0.015、P<；0001和P=0.043)，而12 K-ras基因突变、功能状态和穿孔是OS的独立预后因素(P=0.033、P=0.006和P<；0.0001)。结论：目前的结果为c-Kit过度表达在II期结直肠癌患者中的预后价值提供了证据。P53高突变率和72位密码子的独特热点在结直肠癌中尚未见报道。这可能与研究人群特有的环境或种族特征有关。《癌症》2010年；116：4954--。(C)2010年美国癌症协会
BACKGROUND: The prognosis for patients with colorectal cancer (CRC) depends mainly on standard clinicopathologic factors. However, patients with similar disease characteristics exhibit various outcomes, especially in stage II. Therefore, the identification of molecular prognostic markers is needed to predict patient outcomes. METHODS: The authors assessed the prognostic value of c-Kit (also called cluster of differentiation 117 [CD117] or KIT), cyclooxygenase-2 (COX-2), tumor protein 53 (p53), and Kirsten rat sarcoma viral oncogene homolog (K-ras) aberrations in 90 patients with stage II CRC using immunohistochemistry and molecular techniques. The results were correlated with standard clinicopathologic prognostic factors, overall survival (OS), and disease-free survival (DFS). RESULTS: COX2 and c-Kit overexpression was detected in 54.6% and 59.3% of patients, respectively. Overexpression of p53 was detected in 47 patients, including 29 who had mutations, and a unique mutation pattern was detected with 3 hotspots at codons 72, 245, and 273. Overexpression of ras was detected in 44 patients, including 37 who had mutations. On multivariate analysis, c-Kit overexpression, p53 codon 72 mutations, perforation, and performance status were independent prognostic factors for DFS (P = .054, P = .015, P < .0001, and P = .043, respectively); whereas codon 12 K-ras mutation, performance status, and perforation were independent prognostic factors for OS (P = .033, P = .006, and P < .0001, respectively). CONCLUSIONS: The current results provide evidence for the prognostic value of c-Kit overexpression in patients with stage II CRC. The high p53 mutation rate and the unique hotspot in codon 72 have not been reported previously in CRC. This may be related to environmental or racial features that are unique to the studied population. Cancer 2010;116:4954-64. (C) 2010 American Cancer Society