A retrospective observational study of clinicopathological features of KRAS, NRAS, BRAF and PIK3CA mutations in Japanese patients with metastatic colorectal cancer

BMC Cancer

Akihito Kawazoe¹  Kohei Shitara²  Shota Fukuoka¹  Yasutoshi Kuboki¹  Hideaki Bando¹  Wataru Okamoto²  Takashi Kojima¹  Nozomu Fuse¹  Takeharu Yamanaka³  Toshihiko Doi²  Atsushi Ohtsu²  Takayuki Yoshino² 

[1] Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Chiba, Japan

[2] Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Chiba, Japan

[3] Department of Biostatistics, Yokohama City University, Kanagawa, Japan

关键词: Epidermal growth factor;    PIK3CA;    BRAF;    NRAS;    KRAS;    Colorectal cancer;   

Others  :  1161210
DOI  :  10.1186/s12885-015-1276-z

 received in 2014-09-29, accepted in 2015-03-26,  发布年份 2015

【 摘 要 】

Background

The mutation in KRAS exon 2 is a validated biomarker of resistance to anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (mCRC). Several reports have confirmed associations of other RAS mutations with resistance to anti-EGFR therapy. However, the impact of BRAF and PIK3CA mutations on the efficacy of anti-EGFR therapy remains controversial. Little is known about the frequencies and clinicopathological features of these mutations, as well as the therapeutic effects of anti-EGFR therapy in mCRC patients with these mutations, especially in the Asian population.

Methods

In this retrospective observational study, frequencies and clinicopathological features of KRAS, NRAS, BRAF and PIK3CA mutations were evaluated in patients with mCRC. Among patients treated with anti-EGFR therapy, objective response, progression-free survival (PFS), and overall survival (OS) were evaluated according to gene status.

Results

Among 264 patients, mutations in KRAS exon 2, KRAS exons 3 or 4, NRAS, BRAF and PIK3CA were detected in 34.1%, 3.8%, 4.2%, 5.4% and 6.4%, respectively. Thus, a total of 12.1% of patients without KRAS exon 2 mutations had other RAS mutations. Primary rectal tumors tended to be more frequently observed in RAS mutant tumors. BRAF mutations were more frequently observed with right-sided colon, poorly differentiated or mucinous adenocarcinoma, and peritoneal metastasis. Among the 66 patients with KRAS exon 2 wild-type tumors treated with anti-EGFR agents, PFS (5.8 vs. 2.2 months) and OS (17.7 vs. 5.2 months) were significantly better in patients with all wild-type tumors (n = 56) than in those with any of the mutations (n = 10). The response rate also tended to be better with all wild-type tumors (26.8 vs. 0%).

Conclusion

Other RAS and BRAF mutations were observed in KRAS exon 2 wild-type tumors, which were associated with some clinicopathological features and resistance to anti-EGFR therapy in our patient cohort.

【 授权许可】

   
2015 Kawazoe et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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