Down-regulation of insulin-like growth factor binding protein-5 (IGFBP-5): Novel marker for cervical carcinogenesis

✍ Scribed by Takashi Miyatake; Yutaka Ueda; Ryuichi Nakashima; Kiyoshi Yoshino; Toshihiro Kimura; Takuya Murata; Taisei Nomura; Masami Fujita; Gregory S. Buzard; Takayuki Enomoto

• Book ID: 102863184
• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 585 KB
• Volume: 120
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.22264

✦ Synopsis

Abstract

To better understand the underlying pathways of cervical carcinogenesis, cDNA microarray analysis was performed on 2 sets of squamous cell carcinomas (SCCs) and their adjacent normal squamous epitheliums. Consistently altered expression was detected for 32 genes. Real‐time RT‐PCR analysis was conducted on a selected subset of these genes (S100A2, GPC4, p72, IGFBP‐5, TRIM2 and NAB2) for 14 additional SCCs and 10 normal epithelia. This found that, of the 6 candidate genes, only the insulin‐like growth factor binding protein‐5 (IGFBP‐5) mRNA was generally and significantly under‐expressed in SCCs (p < 0.001). All normal cervical epithelia (30 of 30) stained positively for IGFBP‐5 protein, with 70% showing strong staining, whereas 65% (17/26) of SCC had complete loss of IGFBP‐5, and only 8% (2/26) SCC retained strong expression (p < 0.001). Immunohistochemistry of premalignant cervical intraepithelial neoplasia (CIN) lesions shows a significantly weaker or negative staining in advanced CIN3 lesions compared with normal squamous epithelia (p = 0.001). This is the first study to show that down‐regulation of IGFBP‐5 protein correlates with cervical carcinogenesis and does so at a preneoplastic stage. © 2007 Wiley‐Liss, Inc.