Brief Article
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World J Gastroenterol. Dec 14, 2010; 16(46): 5881-5888
Published online Dec 14, 2010. doi: 10.3748/wjg.v16.i46.5881
Impact of KRAS mutation and PTEN expression on cetuximab-treated colorectal cancer
Fang-Hua Li, Lin Shen, Zhuang-Hua Li, Hui-Yan Luo, Miao-Zhen Qiu, Hui-Zhong Zhang, Yu-Hong Li, Rui-Hua Xu
Fang-Hua Li, Zhuang-Hua Li, Hui-Yan Luo, Miao-Zhen Qiu, Yu-Hong Li, Rui-Hua Xu, State Key Laboratory of Oncology in Southern China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Fang-Hua Li, Department of Medical Oncology, Shengli Oil Field Central Hospital, Dongying 257034, Shandong Province, China
Lin Shen, Department of GI Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, China
Hui-Zhong Zhang, State Key Laboratory of Oncology in Southern China, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Author contributions: Xu RH and Shen L were involved in the design of the study; Li FH, Li ZH, Luo HY and Qiu MZ performed the laboratory assays; Li FH, Luo HY and Li YH were involved in the writing of the article; Zhang HZ coordinated and provided the collection of all the human materials.
Supported by Program for New Century Excellent Talents in University
Correspondence to: Rui-Hua Xu, MD, PhD, State Key Laboratory of Oncology in Southern China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China. xurh@sysucc.org.cn
Telephone: +86-20-87343228 Fax: +86-20-87343228
Received: June 1, 2010
Revised: July 27, 2010
Accepted: August 3, 2010
Published online: December 14, 2010
Abstract

AIM: To investigate the prognostic value of KRAS mutation, and phosphatase and tensin (PTEN) expression in Chinese metastatic colorectal cancer metastatic colorectal cancer (mCRC) patients treated with cetuximab.

METHODS: Ninety Chinese mCRC patients treated with cetuximab were evaluated for KRAS mutation and PTEN protein expression by DNA sequencing of codons 12 and 13 and immunohistochemistry, respectively. We then selected 61 patients treated with cetuximab, either in combination with chemotherapy, or alone as a second-line or third-line regimen to assess whether KRAS mutation or PTEN protein expression is associated with the response and the survival time of mCRC patients treated with cetuximab.

RESULTS: KRAS mutation was found in 30 (33.3%) tumor samples from the 90 patients, and positive PTEN expression was detected in 58 (64.4%) of the 90 patients. Among the 61 patients who were treated with cetuximab as a second-line or third-line regimen, the resistance to cetuximab was found in 22 patients with KRAS mutation and in 39 patients without KRAS mutation, with a response rate of 4.5% and 46.1% respectively (P = 0.001), a shorter median progression-free survival (PFS) time of 14 ± 1.3 wk and 32 ± 2.5 wk respectively (P < 0.001), a median overall survival (OS) time of 11 ± 1.2 mo and 19 ± 1.8 mo respectively (P < 0.001), as well as in 24 patients with negative PTEN expression and in 37 patients with positive PTEN expression respectively (P < 0.001), with a responsive rate of 4.2% and 48.6% respectively, a shorter median PFS survival time of 17 ± 2.0 wk and 28 ± 1.9 wk respectively (P = 0.07), and a median OS time of 11 ± 1.3 mo and 18 ± 1.9 mo respectively (P = 0.004). Combined KRAS mutation and PTEN expression analysis showed that the PFS and OS time of patients with two favorable prognostic factors were longer than those of patients with one favorable prognostic factor or no favorable prognostic factor (P < 0.001).

CONCLUSION: KRAS mutation and PTEN protein expression are significantly correlated with the response rate and survival time of Chinese mCRC patients treated with cetuximab.

Keywords: Cetuximab, Metastatic colorectal cancer, KRAS mutation, Phosphatase and tensin protein expression