Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer

Nakamoto,Kentaro; Nagahara,Hisashi; Maeda,Kiyoshi; Noda,Eiji; Inoue,Toru; Yashiro,Masakazu; Nishiguchi,Yukio; Ohira,Masaichi; Hirakawa,Kosei

doi:10.3892/ol.2013.1187

Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer

Authors:
- Kentaro Nakamoto
- Hisashi Nagahara
- Kiyoshi Maeda
- Eiji Noda
- Toru Inoue
- Masakazu Yashiro
- Yukio Nishiguchi
- Masaichi Ohira
- Kosei Hirakawa
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Affiliations: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan, Department of Gastroenterological Surgery, Osaka City General Hospital, Osaka 545-8585, Japan
Published online on: February 8, 2013 https://doi.org/10.3892/ol.2013.1187
Pages: 1295-1300

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Abstract

Cetuximab (Cmab), a chimeric monoclonal antibody for targeting the epidermal growth factor receptor, has become one of the standard treatments for metastatic colorectal cancer (mCRC). However, only a small proportion of patients respond to Cmab, and it has been reported that KRAS mutation is a negative biomarker of response to Cmab therapy. The aim of this study was to detect additional biomarkers of response to Cmab therapy in patients with mCRC. We evaluated the effects of Cmab therapy in 36 patients with mCRC according to the Response Evaluation Criteria in Solid Tumors, and classified patients who achieved complete response, partial response or stable disease as responders, and patients who achieved progressive disease as non-responders. We retrospectively examined the difference between the two groups using KRAS analysis and immunohistochemistry to determine the expression of E-cadherin, p53 and Ki67. Nineteen patients were responders, while 17 patients were non-responders. KRAS status and expression of E-cadherin were significantly correlated with the effect of Cmab therapy. Moreover, the expression of E-cadherin was significantly correlated with the effect of Cmab therapy in KRAS wild‑type patients. In KRAS mutant-type patients, the expression of E-cadherin did not significantly correlate with the effect of Cmab therapy, but all responders with KRAS mutant-type tumors expressed E-cadherin. Our results indicate that the expression of E-cadherin detected by immunohistochemistry may be a positive predictor of Cmab-based therapy in mCRC, and that a combination of E-cadherin immunohistochemistry and KRAS analysis may be a more sensitive biomarker than KRAS analysis alone.

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