Colorectal Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 7, 2007; 13(5): 699-708
Published online Feb 7, 2007. doi: 10.3748/wjg.v13.i5.699
Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray
Wei-Chang Chen, Mao-Song Lin, Bao-Feng Zhang, Jing Fang, Qiong Zhou, Ying Hu, Heng-Jun Gao
Wei-Chang Chen, Department of Gastroenterology, the First Affiliated Hospital, Soochow University, Suzhou 215006, Jiangsu Province, China
Mao-Song Lin, Department of Gastroenterology, Taizhou People’s Hospital, Taizhou 225300, Jiangsu Province, China
Bao-Feng Zhang, Jing Fang, Qiong Zhou, Ying Hu, Heng-Jun Gao, National Engineering Center for Biochip at Shanghai, Shanghai 201203, China
Author contributions: All authors contributed equally to the work.
Supported by grant from the National 863 Project about Functional Genomic and Biochip, No. 2002AA2Z2021; and 135 Medical Important Talent Foundation of Jiangsu Province, No. 37RC2002037
Correspondence to: Dr. Wei-Chang Chen, Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China. weichangchen@126.com
Telephone: +86-512-65223637-8374 Fax: +86-512-65228072
Received: September 28, 2006
Revised: December 1, 2006
Accepted: December 14, 2006
Published online: February 7, 2007
Abstract

AIM: To explore the molecular events taking place during human colon cancer development and progression through high-throughput tissue microarray analysis.

METHODS: We constructed two separate tissue microarrays containing 1.0 mm or 1.5 mm cylindrical samples acquired from 112 formalin-fixed and paraffin-embedded blocks, including carcinomas (n = 85), adenomatous polyps (n = 18), as well as normal para-cancerous colon tissues (n = 9). Immunohistochemical staining was applied to the analysis of the consecutive tissue microarray sections with antibodies for 11 different proteins, including p53, p21, bcl-2, bax, cyclin D1, PTEN, p-Akt1, β-catenin, c-myc, nm23-h1 and Cox-2.

RESULTS: The protein expressions of p53, bcl-2, bax, cyclin D1, β-catenin, c-myc, Cox-2 and nm23-h1 varied significantly among tissues from cancer, adenomatous polyps and normal colon mucosa (P = 0.003, P = 0.001, P = 0.000, P = 0.000, P = 0.034, P = 0.003, P = 0.002, and P = 0.007, respectively). Chi-square analysis showed that the statistically significant variables were p53, p21, bax, β-catenin, c-myc, PTEN, p-Akt1, Cox-2 and nm23-h1 for histological grade (P = 0.005, P = 0.013, P = 0.044, P = 0.000, P = 0.000, P = 0.029, P = 0.000, P = 0.008, and P = 0.000, respectively), β-catenin, c-myc and p-Akt1 for lymph node metastasis (P = 0.011, P = 0.005, and P = 0.032, respectively), β-catenin, c-myc, Cox-2 and nm23-h1 for distance metastasis (P = 0.020, P = 0.000, P = 0.026, and P = 0.008, respectively), and cyclin D1, β-catenin, c-myc, Cox-2 and nm23h1 for clinical stages (P = 0.038, P = 0.008, P = 0.000, P = 0.016, and P = 0.014, respectively).

CONCLUSION: Tissue microarray immunohistochemical staining enables high-throughput analysis of genetic alterations contributing to human colon cancer development and progression. Our results implicate the potential roles of p53, cyclin D1, bcl-2, bax, Cox-2, β-catenin and c-myc in development of human colon cancer and that of bcl-2, nm23-h1, PTEN and p-Akt1 in progression of human colon cancer.

Keywords: Colon cancer; Immunohistochemistry; Tissue microarray