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菲律宾人前列腺癌晚期 ERG 癌蛋白表达增加。

Increased association of the ERG oncoprotein expression in advanced stages of prostate cancer in Filipinos.

机构信息

Division of Urology, Department of Surgery, College of Medicine, University of the Philippines Manila, Manila, Philippines; Institute of Molecular Biology & Biotechnology, National Institutes of Health, University of the Philippines Manila, Manila, Philippines; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

出版信息

Prostate. 2014 Aug;74(11):1079-85. doi: 10.1002/pros.22791. Epub 2014 Jun 9.

DOI:10.1002/pros.22791
PMID:24909781
Abstract

BACKGROUND

Filipinos with prostate cancer (CaP) are at increased risk of harboring advanced stages and lower survival rates compared to other Asians. This study aims to investigate prevalence of ETS-related gene (ERG) oncoprotein overexpression in Filipinos as surrogate of TMPRSS2-ERG gene fusions, using a highly specific monoclonal antibody (ERG-MAb), and conduct the first attempt to study the role of genetic alterations in the aggressive tumor biologic behaviour of CaP among Filipinos.

METHODS

This case-matched, case-control retrospective study evaluated ERG expression in Filipino patients diagnosed with CaP and its effect on stage and Gleason grade of their disease. Men who underwent radical prostatectomy for organ-confined disease at the University of the Philippines-Philippine General Hospital (UP-PGH) comprised the organ-confined cohort. Age-matched adults who had trans-rectal ultrasound-guided prostate (TRUSP) biopsy or trans-urethral resection of the prostate (TURP) with bilateral orchiectomy for T4 or stage IV CaP composed the advanced disease cohort.

RESULTS

Overall ERG expression frequency of 23.08% (N = 104) was demonstrated, with a higher rate observed in the advanced disease cohort (32.69%) compared to the organ-confined group (13.46%). Furthermore, ERG overexpression was only detected among intermediate and high-risk tumors. A high-specificity (98.08%) of the ERG-MAb for malignant prostatic cells was likewise demonstrated.

CONCLUSIONS

In contrast to higher ERG frequency in Western countries, it is much lower in Filipino CaP, which is similar to lower rates noted from other Asian countries. The 98.08% specificity of ERG oncoprotein for prostate tumor cells combined with its increased association in advanced disease, suggests for prognostic potential of ERG that may aid clinicians in treatment decisions for Filipino CaP patients.

摘要

背景

与其他亚洲人相比,菲律宾前列腺癌(CaP)患者存在更高的晚期风险和更低的生存率。本研究旨在使用高度特异性的单克隆抗体(ERG-MAb)检测 ETS 相关基因(ERG)癌蛋白在菲律宾人中的过表达情况,作为 TMPRSS2-ERG 基因融合的替代物,并首次尝试研究遗传改变在菲律宾人前列腺癌侵袭性肿瘤生物学行为中的作用。

方法

这项病例匹配的病例对照回顾性研究评估了 ERG 在菲律宾前列腺癌患者中的表达及其对疾病分期和 Gleason 分级的影响。在菲律宾大学菲律宾总医院(UP-PGH)接受根治性前列腺切除术的患者组成局限性疾病队列。年龄匹配的接受经直肠超声引导前列腺(TRUSP)活检或经尿道前列腺切除术(TURP)加双侧睾丸切除术治疗 T4 或 IV 期 CaP 的成年人组成晚期疾病队列。

结果

总体上,ERG 表达频率为 23.08%(N=104),在晚期疾病队列中(32.69%)观察到更高的表达率,而在局限性疾病组中(13.46%)观察到更高的表达率。此外,ERG 过表达仅在中高危肿瘤中检测到。还证明了 ERG-MAb 对恶性前列腺细胞的高特异性(98.08%)。

结论

与西方国家更高的 ERG 频率相反,菲律宾 CaP 的频率要低得多,这与其他亚洲国家的低频率相似。ERG 癌蛋白对前列腺肿瘤细胞的 98.08%特异性及其在晚期疾病中的增加关联提示 ERG 具有预后潜力,可能有助于临床医生为菲律宾 CaP 患者做出治疗决策。

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