膀胱癌中的中心体过度扩增与染色体不稳定性

Centrosome hyperamplification and chromosomal instability in bladder cancer.

作者信息

Kawamura K, Moriyama M, Shiba N, Ozaki M, Tanaka T, Nojima T, Fujikawa-Yamamoto K, Ikeda R, Suzuki K

机构信息

Department of Urology, Kanazawa Medical University, 1-1 Daigaku Uchinada, 920-0293, Ishikawa, Japan.

出版信息

Eur Urol. 2003 May;43(5):505-15. doi: 10.1016/s0302-2838(03)00056-3.

DOI:10.1016/s0302-2838(03)00056-3

PMID:12705995

Abstract

OBJECTIVE

Chromosomal instability (CIN) is a common feature of malignant tumors. Centrosome hyperamplification (CH) occurs frequently in human cancers, and may be a contributing factor in CIN. In this study, we investigated the relationship between CH and CIN in bladder cancer.

METHODS

Clinical samples obtained by transurethral resection from 22 patients with bladder cancer were examined (histological grade G1, 5 cases; G2, 6 cases; G3, 11 cases). CH was evaluated by immunohistochemistry using anti-pericentrin antibody. CIN was evaluated by fluorescence in situ hybridization (FISH). FISH probes for pericentromeric regions of chromosomes 3, 7, and 17 were hybridized to touch preparations of nuclei from frozen tissues. We also analyzed the centrosome replication cycle of bladder cancer by laser scanning cytometry (LSC).

RESULTS

Of the 22 cases examined, 18 (81.8%) had centrosome hyperamplification: CH 0, 4 cases (18.1%); CH I, 5 cases (22.7%); CH II, 5 cases (22.7%); CH III, 8 cases (36.4%). The grade of CH was directly proportional to the histological grade (p=0.03, chi(2) test). LSC analysis showed that the centrosome replication cycle was well regulated in pathologically low-grade bladder cancer, which did not have chromosomal instability. In contrast, we found marked variability of centrosomes in pathologically high-grade bladder cancer, which had chromosomal instability. CH and CIN were both detected in pathologically high-grade tumors. The grade of CH was directly proportional to the CIN grade (p=0.0079, chi(2) test).

CONCLUSION

The results of the present study suggest that CH may be involved in CIN in bladder cancer.

摘要

目的

染色体不稳定（CIN）是恶性肿瘤的一个常见特征。中心体过度扩增（CH）在人类癌症中频繁发生，可能是CIN的一个促成因素。在本研究中，我们调查了膀胱癌中CH与CIN之间的关系。

方法

对经尿道切除术获取的22例膀胱癌患者的临床样本进行检查（组织学分级G1，5例；G2，6例；G3，11例）。使用抗中心粒蛋白抗体通过免疫组织化学评估CH。通过荧光原位杂交（FISH）评估CIN。将针对染色体3、7和17着丝粒区域的FISH探针与冷冻组织细胞核的触片进行杂交。我们还通过激光扫描细胞术（LSC）分析了膀胱癌的中心体复制周期。

结果

在检查的22例病例中，18例（81.8%）存在中心体过度扩增：CH 0，4例（18.1%）；CH I，5例（22.7%）；CH II，5例（22.7%）；CH III，8例（36.4%）。CH的分级与组织学分级成正比（p = 0.03，卡方检验）。LSC分析表明，在没有染色体不稳定的病理低级别膀胱癌中，中心体复制周期受到良好调节。相比之下，我们在具有染色体不稳定的病理高级别膀胱癌中发现中心体有明显变异。在病理高级别肿瘤中同时检测到CH和CIN。CH的分级与CIN分级成正比（p = 0.0079，卡方检验）。