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

• Published in: International journal of cancer 2007-05, Vol.120 (10), p.2068-2077
• Main Authors: Miyatake, Takashi, Ueda, Yutaka, Nakashima, Ryuichi, Yoshino, Kiyoshi, Kimura, Toshihiro, Murata, Takuya, Nomura, Taisei, Fujita, Masami, Buzard, Gregory S., Enomoto, Takayuki
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; cDNA microarray; cervical intraepithelial neoplasia (CIN); DNA, Viral - analysis; Down-Regulation; Female; Female genital diseases; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; human papillomavirus (HPV); Human papillomavirus 16 - classification; Human papillomavirus 16 - genetics; Humans; Immunohistochemistry; Insulin-Like Growth Factor Binding Protein 5 - biosynthesis; Insulin-Like Growth Factor Binding Protein 5 - deficiency; Insulin-Like Growth Factor Binding Protein 5 - genetics; insulin‐like growth factor binding protein‐5 (IGFBP‐5); Medical sciences; Neoplasm Staging; Oligonucleotide Array Sequence Analysis - methods; Papillomavirus Infections - genetics; Papillomavirus Infections - metabolism; real‐time RT‐PCR; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; squamous cell carcinoma (SCC); Tumors; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.22264

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.