诊断学理论与实践

诊断学理论与实践 >

2018 , Vol. 17 >Issue 06: 687 - 693

DOI: https://doi.org/10.16150/j.1671-2870.2018.06.012

论著

结肠直肠癌KRAS、NRAS、BRAF基因突变及其与临床病理特征、p53蛋白表达间相关性研究

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  • 上海中医药大学附属曙光医院病理科, 上海 201203

收稿日期: 2018-08-16

  网络出版日期: 2018-12-25

基金资助

国家自然科学基金青年项目（81703885）

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Analysis of KRAS, NRAS and BRAF mutations in colorectal cancer and their correlation with clinicopathologic features and p53 protein expression

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  • Departments of Pathology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Received date: 2018-08-16

  Online published: 2018-12-25

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摘要

目的：筛查肠直肠癌患者的KRAS、NRAS和BRAF基因亚型突变状态, 并分析其与患者临床病理特征及p53蛋白表达情况间的相关性。方法：收集110例手术切除的结肠直肠癌病理资料及组织学样本, 总结临床病理特征;采用突变阻滞扩增系统法检测KRAS、NRAS基因2、3、4号外显子第12、13、61、117、146密码子及BRAF基因15号外显子第600密码子的突变情况;采用免疫组织化学（免疫组化）法检测p53蛋白的表达情况。结果：KRAS基因突变率为45.4%（50/110）, 其中49例患者检测到2号外显子第12和13密码子突变, 1例检测到4号外显子第117和146密码子突变;NRAS基因突变率为6.3%（7/110）, 其中3例检测到2号外显子第12和13密码子突变, 3例检测到3号外显子第61密码子突变, 1例检测到4号外显子第146密码子突变, 且与KRAS基因存在共突变;BRAF基因15号外显子第600密码子突变率为2.7%（3/110）;p53蛋白阳性表达率为57.3%（63/110）, 其中27例患者存在KRAS基因突变, 7例存在NRAS基因突变, 2例存在BRAF基因突变。KRAS基因突变率与患者的淋巴结转移显著相关（P<0.05）;而NRAS基因突变与其组织分型及p53蛋白表达显著相关（P<0.05）;BRAF基因突变率与右半结肠癌显著相关（P<0.05）。结论：KRAS与结肠直肠癌发生、发展的分子机制关系密切;BRAF基因突变仅见于右半结肠, 提示右半结肠癌发生机制可能有其特殊性;p53蛋白表达与NRAS基因突变之间是否存在相互作用关系值得进一步研究。

关键词： 结肠直肠癌; KRAS; NRAS; BRAF; P53

本文引用格式

王子元, 梁婷玉, 陈佳, 韩志宏, 吴丽莉 . 结肠直肠癌KRAS、NRAS、BRAF基因突变及其与临床病理特征、p53蛋白表达间相关性研究[J]. 诊断学理论与实践, 2018 , 17(06) : 687 -693 . DOI: 10.16150/j.1671-2870.2018.06.012

Abstract

Objective: To examine the mutation frequencies of KRAS, NRAS and BRAF in colorectal cancer (CRC) among Chinese population, and to investigate their correlation with clinicopathological parameters and p53 protein expression. Methods: Tissue samples and pathological data of 110 CRC patients undergoing surgical excision were collected, and the clinical pathological features were summarized. Mutations in KRAS (codon 12/13 at exon 2, codon 61 at exon 3 and codon 117/146 at exon 4), NRAS (codon 12/13 at exon 2, codon 61 at exon 3 and codon 146 at exon 4) and BRAF (codon 600 at exon 15) genes were examined with ARMS-PCR. p53 protein expression was detected by immunohistochemistry. Results: 45.4% (50/110) patients carried KRAS mutations; among them, almost all individuals had mutation in KRAS codon 12/13 at exon 2, except one individual had codon 117/146 at exon 4 mutated. 6.3% (7/110) patients carried NRAS mutations; among them, 3/110 patients had mutation in NRAS exon 2 (condon 12/13), 3/110 patients had mutation in NRAS exon 3 (condon 61), 1/110 patient had mutations in both NRAS exon 4 (condon 146) and KRAS. BRAF mutations were detected in 3 patients (2.7%), and were found to have V600E mutations. p53 expression was observed in 63 (57.3%) of 110 CRC patients. Within these 63 positive samples, 27 cases showed KRAS mutations, 7 cases showed NRAS mutations and 2 cases showed BRAF mutations. KRAS mutation was significantly associated with lymph node metastasis (P<0.05) while NRAS mutation was significantly associated with histological type and p53 protein expression (P<0.05). BRAF mutation was significantly associated with right colon cancer (P<0.05). Conclusions: KRAS is closely related to the molecular mechanism of occurrence and development of colorectal cancer. BRAF mutation is only found in right colon cancer, suggesting that the mechanism of right hemicolon cancer may have its particularity. The interaction between p53 protein expression and NRAS mutation is worthy of further study.

Key words： Colorectal cancer; KRAS; NRAS; BRAF; P53

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