端粒酶活性作为印度宫颈上皮内瘤变和宫颈癌女性患者的肿瘤标志物

Telomerase activity as a tumor marker in Indian women with cervical intraepithelial neoplasia and cervical cancer.

作者信息

Sharma Alpana, Rajappa Medha, Saxena Alpana, Sharma Manoj

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Mol Diagn Ther. 2007;11(3):193-201. doi: 10.1007/BF03256241.

DOI:10.1007/BF03256241

PMID:17570741

Abstract

BACKGROUND AND OBJECTIVES

Cervical cancer is the most common cancer in Indian women and is a leading cause of death in women worldwide. Cervical cancer develops from pre-neoplastic cervical intraepithelial neoplasia (CIN). This study was conducted to evaluate telomerase activity as a tumor marker for the detection of cancer in patients with CIN and cervical cancer. The results were compared with human papillomavirus (HPV) status, clinical staging, and histopathologic studies.

METHODS

Telomerase activity was detected using the PCR-based telomeric repeat amplification protocol (TRAP) assay in cervical tissues collected by routine punch biopsy from the uterine cervix of patients with suspected cervical cancer. High-risk (HR) HPV-16 and -18 status was determined in all the study groups, including controls. A total of 125 patients (including 50 patients with CIN and 75 patients with cervical cancer [including nine patients with adeno-squamous disease]) and 22 control subjects were studied. The sensitivity and specificity for detecting CIN and cervical cancer were calculated.

RESULTS

Patients with grade I, II, and III CIN showed 17%, 33%, and 57% positivity for telomerase, respectively. In patients with cervical cancer, those at early clinical stages (Ia-IIb) showed 68% positivity and those at later clinical stages showed 92% positivity for telomerase activity. In the present study, telomerase positivity correlated significantly with the detection of HR HPV-16 and -18 (p < 0.001). As a diagnostic test, none of the described analyses combined a sensitivity of > or =90% with a specificity of > or =90%, except in patients with advanced cancer when telomerase activity was used as a diagnostic test.

CONCLUSION

Our findings suggest that telomerase activation is a relatively early event in cervical carcinogenesis and correlates with the grade of cervical lesion, HR-HPV status (16 and 18 subtypes), and clinical staging. Hence, these associations suggest it as a possible target for detection of cervical cancer.

摘要

背景与目的

宫颈癌是印度女性中最常见的癌症，也是全球女性死亡的主要原因。宫颈癌由癌前病变宫颈上皮内瘤变（CIN）发展而来。本研究旨在评估端粒酶活性作为一种肿瘤标志物，用于检测CIN患者和宫颈癌患者的癌症情况。将结果与人类乳头瘤病毒（HPV）状态、临床分期及组织病理学研究结果进行比较。

方法

采用基于聚合酶链反应（PCR）的端粒重复序列扩增协议（TRAP）分析法，对疑似宫颈癌患者宫颈组织进行常规穿刺活检采集的样本检测端粒酶活性。在所有研究组（包括对照组）中确定高危（HR）HPV - 16和 - 18状态。共研究了125例患者（包括50例CIN患者和75例宫颈癌患者[包括9例腺鳞癌患者]）以及22例对照受试者。计算检测CIN和宫颈癌的敏感性和特异性。

结果

I级、II级和III级CIN患者中端粒酶阳性率分别为17%、33%和57%。在宫颈癌患者中，临床早期（Ia - IIb期）患者端粒酶活性阳性率为68%，临床晚期患者阳性率为92%。在本研究中，端粒酶阳性与HR HPV - 16和 - 18的检测显著相关（p < 0.001）。作为一种诊断测试，除了将端粒酶活性用于晚期癌症患者的诊断测试时，所描述的分析方法均未达到敏感性≥90%且特异性≥90%。