Colorectal Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 28, 2007; 13(28): 3829-3835
Published online Jul 28, 2007. doi: 10.3748/wjg.v13.i28.3829
Immunohistochemical molecular markers as predictors of curability of endoscopically resected submucosal colorectal cancer
Iwao Kaneko, Shinji Tanaka, Shiro Oka, Shigeto Yoshida, Toru Hiyama, Koji Arihiro, Fumio Shimamoto, Kazuaki Chayama
Iwao Kaneko, Kazuaki Chayama, Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Science, Hiroshima, Japan
Shinji Tanaka, Shiro Oka, Shigeto Yoshida, Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
Toru Hiyama, Health Service Center, Hiroshima University, Hiroshima, Japan
Koji Arihiro, Department of Pathology, Hiroshima University Hospital, Hiroshima, Japan
Fumio Shimamoto, Department of Health Science, Prefectural University of Hiroshima, Faculty of Human Culture and Society, Hiroshima, Japan
Author contributions: All authors contributed equally to the work.
Supported by a Grant from the Japanese Society of Gastro-enterological Endoscopy, Chugoku Branch
Correspondence to: Shinji Tanaka, MD, PhD, Department of Endoscopy, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. colon@hiroshima-u.ac.jp
Telephone: +81-82-2575538 Fax: +81-82-2575538
Received: March 15, 2007
Revised: April 23, 2007
Accepted: April 26, 2007
Published online: July 28, 2007
Abstract

AIM: To clarify the usefulness of immunohistochemical molecular markers in predicting lymph node metastasis of submucosal colorectal cancer.

METHODS: We examined microvessel density, lymphatic vessel density, the Ki-67 labeling index, expression of MUC1 and Matrix metalloproteinase-7 (MMP-7) in tumor cells, and expression of cathepsin D in stromal cells at the invasive front by immunostaining of samples resected from 214 patients with submucosal colorectal cancer. Pathologic features were assessed on hematoxylin-eosin-stained samples. We evaluated the relations between clinicopathologic/immunohistochemical features and lymph node metastasis.

RESULTS: Lesions of the superficial type, with an unfavorable histologic grade, budding, lymphatic involvement, high microvessel density (≥ 40), high lymphatic vessel density (≥ 9), high Ki-67 labeling index (≥ 42), and positivity of MUC1, cathepsin D, and MMP-7 showed a significantly high incidence of lymph node metastasis. Multivariate analysis revealed that high microvessel density, unfavorable histologic grade, cathepsin D positivity, high lymphatic vessel density, superficial type, budding, and MUC1 positivity were independent risk factors for lymph node metastasis. A combined examination with four independent immunohistochemical markers (microvessel density, cathepsin D, lymphatic vessel density, and MUC1) revealed that all lesions that were negative for all markers or positive for only one marker were negative for lymph node metastasis.

CONCLUSION: Analysis of a combination of immuno-histochemical molecular markers in endoscopically resected specimens of submucosal colorectal cancer allows prediction of curability regardless of the pathologic features visible of hematoxylin-eosin-stained sections.

Keywords: Submucosal colorectal cancer; Microvessel density; Lymphatic vessel density; Mucin 1; Ki-67; Cathepsin D; Matrix metalloproteinase-7; Lymph node metastasis; Immunohistochemistry