Associations of positive epidermal growth factor receptor expression and K-RAS gene mutations with various clinicopathological parameters and survival of colorectal carcinoma patients

Warsinggih Warsinggih , Irawan Yusuf , Ida Bagus Tjakra Wibawa Manuaba , Aryono Pusponegoro
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引用次数: 2

Abstract

Epidermal growth factor receptor (EGFR) is a member of the transmembrane receptor tyrosine kinase family. In normal and malignant cells, activation of the EGFR cascade is involved in the regulation of various cellular activities. The objective of this study was to identify and assess associations of positive EGFR expression and K-RAS mutations with various clinicopathological parameters and survival of colorectal carcinoma patients. EGFR of colorectal cancer (CRC) tissue specimens was subjected to immunohistochemical analysis, polymerase chain reaction, and DNA sequencing. Immunohistochemical staining was performed using monoclonal antibodies against EGFR antigens and examination of mutations was performed to detect mutations in codons 12 and 13 of the K-RAS. Statistical analysis was performed using SPSS version 16.0. The results of this study showed that of the 40 study participants, 62.5% (25/40) showed positive EGFR overexpression. Of the patients showing positive EGFR expressions, 52% had mutations in the K-RAS. Mutations were spread in codon 12 (64.3%) and codon 13 (35.7%) and there was one sample with mutations in codons 12 and 13 at the same time. A statistically significant association was found between the presence of metastasis and EGFR overexpression and survival of CRC patients. In addition, a significant association was found between K-RAS mutations and metastasis and survival of CRC patients. In conclusion, EGFR overexpression and K-RAS mutations were found in CRC patients. Both factors are known to be associated with poor prognosis of cancer patients in terms of patient survival. Early detection of K-RAS mutations in CRC patients is a crucial component in the determination of the type of therapy and treatment for the patient.

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表皮生长因子受体阳性表达和K-RAS基因突变与结直肠癌患者各种临床病理参数和生存的关系
表皮生长因子受体(EGFR)是跨膜受体酪氨酸激酶家族的一员。在正常和恶性细胞中,EGFR级联的激活参与各种细胞活动的调节。本研究的目的是确定和评估EGFR阳性表达和K-RAS突变与结直肠癌患者各种临床病理参数和生存的关系。对结直肠癌(CRC)组织标本的EGFR进行免疫组化分析、聚合酶链反应和DNA测序。使用抗EGFR抗原的单克隆抗体进行免疫组化染色,并进行突变检测,检测K-RAS的密码子12和13的突变。采用SPSS 16.0进行统计分析。本研究结果显示,在40名研究参与者中,62.5%(25/40)显示EGFR阳性过表达。在EGFR阳性表达的患者中,52%的患者有K-RAS突变。突变分布在密码子12(64.3%)和密码子13(35.7%),同时有1份样本存在密码子12和13的突变。转移的存在与EGFR过表达与结直肠癌患者的生存之间存在统计学意义上的相关性。此外,K-RAS突变与结直肠癌患者的转移和生存存在显著相关性。结论:结直肠癌患者存在EGFR过表达和K-RAS突变。已知这两个因素都与癌症患者预后不良有关。早期发现结直肠癌患者的K-RAS突变是确定患者治疗类型和治疗的关键组成部分。
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