血清血管内皮细胞生长因子C(VEGF-C)是晚期宫颈癌的特异性生物标记物:VEGF-C与胰岛素样生长因子Ⅱ(IGF-Ⅱ)、IGF结合蛋白3(IGF-BP3)及血管内皮细胞生长因子B(VEGF-B)的关系

作     者：Mathur S.P. Mathur R.S. Gray E.A. 朱国栋 

作者机构：Department of Obstetrics and Gynecology Hollings Cancer Society Medical University of South Carolina 96 Jonathan Lucas Street Charleston SC 29425 United States 

出 版 物：《世界核心医学期刊文摘（妇产科学分册）》 (Core Journal in Obstetrics/Gynecology)

年 卷 期：2005年第1卷第12期

页      面：51-53页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：IGF-BP3 晚期宫颈癌 IGF-Ⅱ VEGF-B 特异性指标 生物标记物 早期宫颈癌 结合蛋白 非典型鳞状细胞 上皮内瘤 

摘      要：Objectives. An early non- invasive diagnosis of cervical cancer and its metastasis can save lives. We have shown that serum IGF- II levels can be effectively used for a specific early diagnosis of cervical cancer. Here, we shall determine if serum levels of vascular endothelial growth factors B and C (VEGF- B, VEGF- C) associated with vasculogenic and lymphogenic metastasis may be used for an early diagnosis of advanced metastatic cervical cancer and compare these levels with those of the serum IGF- II and IGF- binding protein 3 (IGF- BP3). Material and methods. (a) Serum levels of IGF- II, IGF- BP3, VEGF- B (VEGF 165)and VEGF- C (ELISA kits) were determined in: 82 controls with normal Pap smears; 29 women with atypical squamous cells of undetermined significance (ASCUS) and normal cervical biopsy; 46 ASCUS and cervical intraepithelial neoplasia (CIN) on biopsy; 8 pre-therapy CIN- I; 23 successfully treated CIN- I; 75 persistent CIN- I; 14 CIN- II/III pre-therapy; 14 successfully treated CIN- II/III; 70 persistent CIN- II/III; 86 pre-therapy cervical cancer; 26 in early grades of cervical cancer; 21 in late grades of cervical cancer; 22 cervical cancer patients in remission; 50 persistent cervical cancer; 18 with ovarian cancer; and 57 with endometrial cancer. (b) Serial serum samples collected over 5 years in 5 women with progressing cervical cancer were also tested. (c) Serum and tissue VEGF- C were enumerated in 20 matched serum (ELISA) and tissue (semi-quantitative immunofluorescent antibody assay) samples from controls, early cervical cancer, late cervical cancer, ovarian cancer and endometrial cancer patients. Student s t test, chi-square analysis and linear regression analysis were used. Results. (a) As anticipated, serum IGF- II levels were elevated as early as ASCUS with CIN on biopsy and continued to be elevated in CIN (all grades; pre-therapy and persistent) and cervical cancer (pre-therapy, early, late and persistent). Serum IGF- II levels were normal in ASCUS with normal biopsy, successfully treated CIN- I, II/III, cervical cancer as well as pre-therapy ovarian and endometrial cancers (therapy efficacy: P 0.0001 by chi-square analysis). Serum IGF- BP3 showed a significant decrease with advancing disease. Serum VEGF- B levels were the highest in pre-therapy, early, advanced and persistent cervical cancer, as well as in ovarian and endometrial cancers. Serum VEGF- C levels, on the other hand, were the highest in late and persistent cervical cancers, but not in ovarian or endometrial cancers. (b) In the 5 women with serial samples, the serum levels of the growth factors showed similar trends. (c) VEGF- C levels in serum and tissue were elevated in cervical cancers especially in advanced grades, while they were normal in serum and tissue from the controls and women with ovarian and endometrial cancers. There was a highly significant positive correlation between VEGF- C and IGF- II and a negative correlation between IGF- BP3 and VEGF- C (P 0.0001). Conclusion. Serum IGF- II up- regulation is specific to cervical cancer and helps in the early diagnosis of malignant proliferation, while serum VEGF- C up- regulation appears to be a unique marker for an early diagnosis of cervical cancer metastasis. VEGF- C and IGF- II systems appear to be interrelated in cervical cancer, contributing to the early malignant cell proliferation and lympho-vascular metastasis. Serum IGF- BP3 and VEGF- B appear to be common markers for all gynecological cancers.