上皮細胞生長因子受體表現陽性之結腸直腸癌患者KRAS突變成行率

The Prevalence of KRAS Gene Mutation in Colorectal Cancer Patients with Epidermal Growth Factor Receptor Expression

標靶藥物療法通常用於治療結腸直腸癌患者。臨床上，結腸直腸癌組織KRAS基因突變狀態可以決定是否能夠接受對抗上皮細胞生長因子受體（epidermal growth factor receptor, EGFR）之標靶藥物治療的選擇之一。本研究要探討台灣目前在上皮細胞生長因子受體陽性的結腸直腸癌組織中，KRAS基因突變的盛行率。分析在台北馬偕醫院已接受治療的164例結腸直腸癌患者（平均年齡61.80±12.78年）。癌瘤組織經免疫化學染色法測定後，選出48例癌瘤組織中EGFR表現陽性樣本，再經桑格（Sanger）定序法分析癌瘤組織中KRAS基因突變狀態。結果在48例癌瘤組織樣本中發現有高達50%之KRAS基因在密碼子12和13上出現突變現象，並且有41.67%是發生在轉移性結腸直腸癌患者組織上。KRAS基因密碼子12的突變率有75.00%，特別是甘氨酸轉成天門冬氨酸（G12D，50.00%）和甘氨酸轉成纈氨酸（G12V，12.50%）。KRAS基因密碼子13突變率有25.00%，主要是甘氨酸轉成天門冬氨酸（G13D，25.00%）。本研究發現有高的KRAS基因突變率出現在EGFR表現陽性的結腸直腸癌組織中。

Anti-epidermal growth factor receptor targeted therapy is typically used to treat colorectal cancer (CRC). The KRAS gene status is one of eligible situations for treating CRC patients with targeting drugs. This study was to clarify the recent prevalence of KRAS gene mutation in CRC patients with epidermal growth factor receptor (EGFR) expression in Taiwan. One hundred and sixty-four patients (mean age, 61.80±12.78 years) who suffered from CRC were enrolled in this study at Mackay Memorial Hospital in Taiwan. Among those CRC paraffin-embedded tissues, 48 subjects with EGFR expression were detected by immunohistochemical method, and those Kirsten RAS (KRAS) gene were amplified using the Sanger sequencing method. The KRAS mutations in codons 12 and 13 were found in 50.00% of all EGFR-expressing CRC patients, and in 41.67% of metastatic CRC patients. The most frequent mutations were those on codon 12 (75.00%), especially glycine-to-aspartate (G12D, 50.00%) and glycine-to-valine (G12V, 12.50%) mutations. A 25.00% mutation on codon 13 was mostly glycine-to-aspartate (G13D, 25.00%). This study identified a high frequency of KRAS somatic mutation in CRC with EGFR expressed patients.