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用于分子分期的多标志物实时逆转录聚合酶链反应定量检测黑色素瘤相关抗原:一项5年研究的结果

Quantitative detection of melanoma-associated antigens by multimarker real-time RT-PCR for molecular staging: results of a 5 years study.

作者信息

Gkalpakiotis Spyridon, Arenberger Petr, Kremen Jaromir, Arenbergerova Monika

机构信息

Department of Dermatovenereology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.

出版信息

Exp Dermatol. 2010 Nov;19(11):994-9. doi: 10.1111/j.1600-0625.2010.01123.x. Epub 2010 Aug 31.

DOI:10.1111/j.1600-0625.2010.01123.x
PMID:20812969
Abstract

INTRODUCTION

Monitoring of circulating melanoma cells in the peripheral blood is a promising method for identifying a subgroup of patients with minimal residual disease.

OBJECTIVES

To evaluate the prognostic impact of melanoma-associated antigens by multimarker real-time RT-PCR for disease-specific survival time.

METHODS

Five melanoma markers: Melan-A, gp 100, MAGE-3, MIA and tyrosinase were detected by a quantitative multimarker real-time reverse transcription-PCR (RT-PCR). We included 65 patients with resected melanoma in stage II-III. Peripheral blood samples were examined every 3 months for 2 years. The expression of melanoma markers in 2925 RT-PCR assays was correlated with clinical staging results in total of 5 years.

RESULTS

Twenty-seven patients relapsed during the study period and 26 of them revealed positive markers. MAGE-3 was the most sensitive progression marker in single occurrence or in combination with MIA and gp 100. The time distribution of metastases during the screened period was as follows: progression in the first year was observed in 40.7% patients, second year in 25.9%, third year in 18.6%, fourth and fifth year in 7.4% equally.

CONCLUSIONS

Statistically significant tumor marker elevation during the first 2 years after the surgical treatment correlates with a worse prognosis of patients. In contrast, the group showing negative real-time RT-PCR results in 24 months serial blood testing was associated with prolonged 5-year disease-specific survival. Therefore, quantitative detection of melanoma-specific molecular markers in the presented setting represents a useful tool for selecting patients in a higher risk of disease recurrence.

摘要

引言

监测外周血中循环黑色素瘤细胞是识别微小残留病患者亚组的一种有前景的方法。

目的

通过多标志物实时逆转录聚合酶链反应(RT-PCR)评估黑色素瘤相关抗原对疾病特异性生存时间的预后影响。

方法

采用定量多标志物实时逆转录聚合酶链反应(RT-PCR)检测五种黑色素瘤标志物:黑色素A、糖蛋白100、黑色素瘤抗原基因-3(MAGE-3)、黑色素瘤抑制活性蛋白(MIA)和酪氨酸酶。我们纳入了65例II-III期黑色素瘤切除患者。每3个月采集外周血样本,持续2年。2925次RT-PCR检测中黑色素瘤标志物的表达与5年的临床分期结果相关。

结果

27例患者在研究期间复发,其中26例显示标志物阳性。MAGE-3是单独出现或与MIA和糖蛋白100联合时最敏感的进展标志物。筛查期间转移的时间分布如下:第一年进展的患者占40.7%,第二年占25.9%,第三年占18.6%,第四年和第五年各占7.4%。

结论

手术治疗后前2年肿瘤标志物有统计学意义的升高与患者预后较差相关。相比之下,在连续24个月的血液检测中实时RT-PCR结果为阴性的组与延长的5年疾病特异性生存相关。因此,在本研究中定量检测黑色素瘤特异性分子标志物是选择疾病复发风险较高患者的有用工具。

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