Mathur Subbi P, Mathur Rajesh S, Creasman Willaim T, Underwood Paul B, Kohler Matthew
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA.
Cancer Biomark. 2005;1(2-3):183-91. doi: 10.3233/cbm-2005-12-306.
Cervical cancer is a major gynecologic malignancy around the world. However, current diagnostic methods such as Pap smear and human papilloma virus (HPV) testing are insufficient for an early diagnosis of cervical cancer, follow-up on therapy efficacy or to identify the women who might progress to cervical cancer (only about 1-5% of the HPV-positive women will develop cervical cancer). Patients with atypical squamous cells of undetermined significance (ASC-US) clearly need a better screening test. Developing a non-invasive method for early diagnosis of cervical cancer is essential. Our in vitro and translational research data support the hypothesis that: 1. Squamous cell cervical cancer is related to specific upregulation of tissue and serum Insulin-like Growth Factor-II levels (IGF-II; 100% sensitivity and 100% specificity). Serum IGF-I, but not IGF-II levels are elevated in other gynecological, breast, lung and prostate cancers. Serum IGF-II test helps in diagnosing cervical cancer as early as ASC-US or cervical intraepithelial neoplasia (CIN)-I and in monitoring therapy efficacy (p < 0.001 by Student's 't' test and Chi-square analysis). 2. Concomittant to increased serum IGF-II levels, IGF-Binding Protein 3 (IGF-BP3) levels are significantly decreased in persistent CIN and cervical cancer (p < 0.0001). As IGF-BP3 modulates IGF-II biological activity, significantly decreased serum IGF-BP3 levels (levels normalize after therapy; p < 0.001) may indicate a poor prognosis. Similar to serum IGF-II, serum IGF-BP3 levels help monitoring therapy efficacy in cervical cancer and advanced CIN. Measurement of serum IGF-II levels will help in early diagnosis of cervical cancer and monitoring of therapy outcome. Serum IGF-BP3 in conjunction with IGF-II levels may help in predicting prognosis as well as monitoring therapy efficacy.
宫颈癌是全球主要的妇科恶性肿瘤。然而，目前的诊断方法，如巴氏涂片检查和人乳头瘤病毒（HPV）检测，对于宫颈癌的早期诊断、治疗效果的随访或识别可能进展为宫颈癌的女性来说并不充分（只有约1-5%的HPV阳性女性会发展为宫颈癌）。意义不明确的非典型鳞状细胞（ASC-US）患者显然需要更好的筛查检测方法。开发一种用于宫颈癌早期诊断的非侵入性方法至关重要。我们的体外和转化研究数据支持以下假设：1. 宫颈鳞状细胞癌与组织和血清胰岛素样生长因子-II水平（IGF-II）的特定上调有关（敏感性100%，特异性100%）。在其他妇科、乳腺癌、肺癌和前列腺癌中，血清IGF-I水平升高，但IGF-II水平不升高。血清IGF-II检测有助于早在ASC-US或宫颈上皮内瘤变（CIN）-I阶段诊断宫颈癌，并监测治疗效果（通过学生t检验和卡方分析，p<0.001）。2. 与血清IGF-II水平升高相伴的是，持续性CIN和宫颈癌中胰岛素样生长因子结合蛋白3（IGF-BP3）水平显著降低（p<0.0001）。由于IGF-BP3调节IGF-II的生物学活性，血清IGF-BP3水平显著降低（治疗后水平恢复正常；p<0.001）可能预示预后不良。与血清IGF-II类似，血清IGF-BP3水平有助于监测宫颈癌和高级别CIN的治疗效果。测量血清IGF-II水平将有助于宫颈癌的早期诊断和治疗结果的监测。血清IGF-BP3与IGF-II水平结合可能有助于预测预后以及监测治疗效果。
