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前列腺癌的诊断生物标志物。

Diagnostic biomarkers of prostate cancer.

作者信息

Häggarth Lars, Hägglöf Christina, Jaraj Sara Jonmarker, Wester Kenneth, Pontén Fredrik, Ostman Arne, Egevad Lars

机构信息

Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

出版信息

Scand J Urol Nephrol. 2011 Feb;45(1):60-7. doi: 10.3109/00365599.2010.526141. Epub 2010 Nov 1.

DOI:10.3109/00365599.2010.526141
PMID:21034352
Abstract

OBJECTIVE

Diagnostic tissue biomarkers for prostate cancer (PC) include basal cell markers and α-methylacyl-coenzyme A-racemase (AMACR), often used in combination. Their sensitivity and specificity are not perfect and there is a need for additional diagnostic biomarkers for PC in cases that are difficult to diagnose on routine stained sections.

MATERIAL AND METHODS

This study investigated the diagnostic accuracy of three novel tissue biomarkers for PC found through a search in the Human Protein Atlas database ( www.proteinatlas.com ): somatic cytochrome c (CYCS), intestinal cell kinase (ICK) and inhibitor of nuclear factor-κB kinase subunit beta (IKBKB), and compared the results with AMACR. A tissue microarray was constructed from 40 consecutive radical prostatectomy (RP) specimens including benign prostatic tissue, atrophy, high-grade prostatic intraepithelial neoplasia (HGPIN) and PC. Immunoreactivity was scored based on staining intensity and extent. Real-time polymerase chain reaction (PCR) was performed on malignant and benign frozen tissue samples from 32 RP specimens.

RESULTS

All four biomarkers showed a stronger expression in PC and HGPIN than in benign tissue (p < 0.001). The highest diagnostic accuracy for PC was achieved with ICK and AMACR at 97%. The area under the curve for CYCS, ICK, IKBKB and AMACR was 0.859, 0.997, 0.865 and 0.983, respectively. The presence of mRNA transcripts of the genes was confirmed by real-time PCR in benign and malignant prostatic tissue.

CONCLUSIONS

AMACR is an accurate diagnostic tissue marker for PC. However, in some PCs AMACR is false negative and a panel of CYCS, ICK and IKBKB may serve as ancillary diagnostic tool.

摘要

目的

前列腺癌(PC)的诊断组织生物标志物包括基底细胞标志物和α-甲基酰基辅酶A消旋酶(AMACR),二者常联合使用。它们的敏感性和特异性并不理想,对于常规染色切片难以诊断的PC病例,需要额外的诊断生物标志物。

材料与方法

本研究通过检索人类蛋白质图谱数据库(www.proteinatlas.com),研究了三种新型PC组织生物标志物的诊断准确性:体细胞细胞色素c(CYCS)、肠细胞激酶(ICK)和核因子κB激酶亚基β抑制剂(IKBKB),并将结果与AMACR进行比较。从40例连续的根治性前列腺切除术(RP)标本构建组织芯片,包括良性前列腺组织、萎缩、高级别前列腺上皮内瘤变(HGPIN)和PC。根据染色强度和范围对免疫反应性进行评分。对32例RP标本的恶性和良性冷冻组织样本进行实时聚合酶链反应(PCR)。

结果

所有四种生物标志物在PC和HGPIN中的表达均强于良性组织(p < 0.001)。ICK和AMACR对PC的诊断准确性最高,为97%。CYCS、ICK、IKBKB和AMACR的曲线下面积分别为0.859、0.997、0.865和0.983。通过实时PCR在良性和恶性前列腺组织中证实了这些基因的mRNA转录本的存在。

结论

AMACR是PC的一种准确的诊断组织标志物。然而,在一些PC病例中AMACR为假阴性,CYCS、ICK和IKBKB组合可能作为辅助诊断工具。

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