1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Mod Pathol. 2010 Mar;23(3):359-66. doi: 10.1038/modpathol.2009.134. Epub 2010 Jan 8.
Giant cell tumour of bone, a benign but potentially aggressive neoplasm, shows an increasing rate of chromosomal aneusomy that correlates with clinical course. Mechanisms that generate chromosomal instability in giant cell tumour of bone are poorly understood. One possible cause of chromosomal instability is an error in mitotic segregation due to numeric and/or functional abnormalities of centrosomes. Centrosome alteration is a common phenomenon in many cancers and has a major role in the development of chromosomal instability in cancer cells. To gain an insight into the possible mechanism for the generation of chromosomal instability in giant cell tumour of bone, we analysed 100 cases, including 57 primary nonrecurrent, 35 recurrent and 8 malignant giant cell tumour of bone cases. gamma-Tubulin immunohistochemistry was performed on tissue microarrays of 59 formalin-fixed paraffin-embedded cases, whereas pericentrin and gamma-tubulin fluorescent immunocytochemistry was carried out on 41 frozen smears. Fluorescent in situ hybridization was performed on 23 cases of pericentrin immunostained smears, allowing the simultaneous analysis of centrosomes and chromosome aberrations. Centrosome amplification was significantly higher in recurrent and malignant giant cell tumour of bones compared with nonrecurrent tumours (P<0.001). A comparison of the percentage of aneusomic cells with a normal centrosome content (4.7%) with that of aneusomic cells with centrosome amplification (6.4%) revealed no significant association between chromosome number alterations and centrosome aberrations (P=0.31). These findings indicate that centrosome alteration and frequency of aneusomy correlate with clinical behaviour; the lack of an association between centrosome amplification and chromosome number alteration suggests that alternative causative mechanisms produce genetic instability in giant cell tumour of bone.
骨巨细胞瘤是一种良性但具有潜在侵袭性的肿瘤，其染色体非整倍体率逐渐增加，且与临床病程相关。导致骨巨细胞瘤染色体不稳定性的机制尚不清楚。染色体不稳定性的一个可能原因是由于中心体的数量和/或功能异常导致有丝分裂分离错误。中心体改变是许多癌症中的常见现象，在癌细胞的染色体不稳定性发展中起着重要作用。为了深入了解骨巨细胞瘤中染色体不稳定性产生的可能机制，我们分析了 100 例病例，包括 57 例原发性非复发性、35 例复发性和 8 例恶性骨巨细胞瘤病例。对 59 例福尔马林固定石蜡包埋组织微阵列进行了γ微管蛋白免疫组化分析，对 41 例冷冻涂片进行了中心体蛋白和γ微管蛋白荧光免疫细胞化学分析。对 23 例经中心体蛋白免疫染色的涂片进行了荧光原位杂交，允许同时分析中心体和染色体异常。与非复发性肿瘤相比，复发性和恶性骨巨细胞瘤中的中心体扩增明显更高（P<0.001）。将具有正常中心体含量（4.7%）的非整倍体细胞的百分比与具有中心体扩增的非整倍体细胞（6.4%）进行比较，发现染色体数目改变与中心体异常之间没有显著相关性（P=0.31）。这些发现表明中心体改变和非整倍体频率与临床行为相关；中心体扩增与染色体数目的改变之间缺乏关联表明，在骨巨细胞瘤中产生遗传不稳定性的是替代性的致病机制。
