演題抄録

International Session

開催概要
開催回
第55回・2017年・横浜
 

抗EGFR抗体薬マーカーとしてのAmphiregulin発現と大腸癌腫瘍局在部位との関連性の検討

演題番号 : IS6-5

[筆頭演者]
倉持 英和:1 
[共同演者]
中島 豪:2、林 和彦:2、山本 雅一:3、片桐 聡:4、新井田 達雄:4

1:東京女子医科大学・八千代医療センター・化学療法科、2:東京女子医科大学・病院・化学療法・緩和ケア科、3:東京女子医科大学・病院・消化器・一般外科、4:東京女子医科大学・八千代医療センター・消化器外科

 

Background: Left-sided colon cancer has been reported to be more sensitive to anti-EGFR antibody than right-sided, although the mechanism is not well investigated. Amphiregulin (AREG) and Epiregulin (EREG) are EGFR ligands whose mRNA expression levels were reported to be effective predictive biomarkers for anti-EGFR antibody.
Methods: We investigated 157 metastatic colorectal cancer (CRC) patients who underwent primary tumor resection at our institute (102 were KRAS codon 12,13 wild-type, while 55 patients had oncogenic KRAS mutations). AREG and EREG mRNA levels were measured using real-time RT-PCR from paraffin embedded samples.
Results: Among KRAS wild-type patients, the frequency of high AREG expression in left-sided was significantly higher than in right-sided CRC (left: high vs. low = 40:31, right: high vs. low = 10:21, p = 0.025). However, no associations between AREG or EREG expression levels and tumor location were observed among patients with KRAS-mutated cancer (left: high vs. low = 14:18, right: high vs. low = 11:12, p = 0.76). Among KRAS wild-type patients, 37 received anti-EGFR antibody, and the proportion with high AREG expression was significantly higher in left-sided than right-sided CRC (left: AREG high vs. low = 19:7, right: AREG high vs. low = 2:9, p=0.0034). The response rates were 47.6% in AREG-high patients and 28.0% in AREG-low patients with left-sided CRC, while response rates were 50% in AREG-high and 0% in AREG-low right-sided CRC. Overall survival (OS) of left-sided CRC was significantly longer in patients with high EREG levels than those with low EREG levels (Median survival time: not reached vs. 199 d, p=0.018), although no OS difference was observed between patients with high EREG levels and those with low EREG levels in right-sided CRC (p=0.46).
Conclusion: AREG and EREG mRNA expression levels in left-sided CRC were higher than in right-sided disease. This may be the reason for the higher efficacy of anti-EGFR therapy in left-sided CRC.

キーワード

臓器別:大腸・小腸

手法別:バイオマーカー

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