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凋亡抑制蛋白家族成员survivin在膀胱癌中的表达及抗原性:对特异性免疫治疗的意义

Expression and antigenicity of survivin, an inhibitor of apoptosis family member, in bladder cancer: implications for specific immunotherapy.

作者信息

Kitamura Hiroshi, Torigoe Toshihiko, Honma Ichiya, Asanuma Hiroko, Nakazawa Emiri, Shimozawa Kumiko, Hirohashi Yoshihiko, Sato Eiji, Sato Noriyuki, Tsukamoto Taiji

机构信息

Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.

出版信息

Urology. 2006 May;67(5):955-9. doi: 10.1016/j.urology.2005.11.052. Epub 2006 Apr 25.

Abstract

OBJECTIVES

To assess the expression of survivin in transitional cell carcinoma of the bladder and to study whether survivin is a transitional cell carcinoma-specific antigen that could be a target for immunotherapy. Survivin, an inhibitor of apoptosis family member, has been reported to be expressed in various cancers but not in normal adult tissues.

METHODS

Immunohistochemical staining for survivin and human leukocyte antigen (HLA) class I was performed on specimens from 88 patients who underwent transurethral resection and radical cystectomy. To determine whether survivin was recognized as a tumor antigen by the host immune system, we assessed anti-survivin antibodies in the sera of 52 patients and 18 healthy volunteers with an enzyme-linked immunosorbent assay using recombinant survivin.

RESULTS

Survivin and HLA class I were expressed in 77 (87.5%) and 59 (67.0%) of the 88 bladder cancer specimens, respectively, and 56 (63.6%) expressed both survivin and HLA class I. The absorbance values of anti-survivin antibodies in patients with bladder cancer were significantly greater than those in the healthy volunteers. A relationship was found between the level of serum anti-survivin antibodies and the staining intensity of survivin in the specimen.

CONCLUSIONS

Survivin is expressed in carcinoma of the bladder with high sensitivity. It is suggested that survivin is presented on HLA class I molecules of antigen-presenting cells in 64% of patients with bladder cancer. Therapeutic targeting of survivin in bladder cancer is a future possibility.

摘要

目的

评估生存素在膀胱移行细胞癌中的表达,并研究生存素是否为可作为免疫治疗靶点的膀胱移行细胞癌特异性抗原。生存素是凋亡抑制蛋白家族成员,据报道在多种癌症中表达,但在正常成人组织中不表达。

方法

对88例行经尿道切除术和根治性膀胱切除术患者的标本进行生存素和人类白细胞抗原(HLA)-I类免疫组化染色。为确定生存素是否被宿主免疫系统识别为肿瘤抗原,我们用重组生存素通过酶联免疫吸附试验评估了52例患者和18名健康志愿者血清中的抗生存素抗体。

结果

88例膀胱癌标本中,生存素和HLA-I类分别在77例(87.5%)和59例(67.0%)中表达,56例(63.6%)同时表达生存素和HLA-I类。膀胱癌患者抗生存素抗体的吸光度值显著高于健康志愿者。血清抗生存素抗体水平与标本中生存素染色强度之间存在相关性。

结论

生存素在膀胱癌中高表达。提示在64%的膀胱癌患者中,生存素在抗原呈递细胞的HLA-I类分子上呈递。针对膀胱癌中生存素的治疗靶向是未来的一种可能性。

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