title: Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer.
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 thatKRASmutation 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 usingKRASanalysis and immunohistochemistry to determine the expression of E-cadherin, p53 and Ki67. Nineteen patients were responders, while 17 patients were non-responders.KRASstatus 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 inKRASwild-type patients. InKRASmutant-type patients, the expression of E-cadherin did not significantly correlate with the effect of Cmab therapy, but all responders withKRASmutant-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 andKRASanalysis may be a more sensitive biomarker thanKRASanalysis alone.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakamoto
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nagahara
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Maeda
authors.forename: Eiji
authors.initials: E
authors.lastname: Noda
authors.forename: Toru
authors.initials: T
authors.lastname: Inoue
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yashiro
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nishiguchi
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ohira
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
keywords: E-cadherin; KRAS mutation; biomarker; cetuximab; mCRC