TY - JOUR
T1 - Centrosome abnormalities in giant cell tumour of bone
T2 - Possible association with chromosomal instability
AU - Moskovszky, Linda
AU - Dezsö, Katalin
AU - Athanasou, Nick
AU - Szendröi, Miklós
AU - Kopper, László
AU - Kliskey, Karolina
AU - Picci, Piero
AU - Sápi, Zoltán
PY - 2010/3
Y1 - 2010/3
N2 - 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. γ-Tubulin immunohistochemistry was performed on tissue microarrays of 59 formalin-fixed paraffin-embedded cases, whereas pericentrin and γ-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 (P0.001). 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 (P0.31). 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.
AB - 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. γ-Tubulin immunohistochemistry was performed on tissue microarrays of 59 formalin-fixed paraffin-embedded cases, whereas pericentrin and γ-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 (P0.001). 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 (P0.31). 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.
KW - Aneusomy
KW - Centrosome chromosomal instability
KW - Giant cell tumour of bone
KW - Predictive factor
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U2 - 10.1038/modpathol.2009.134
DO - 10.1038/modpathol.2009.134
M3 - Article
C2 - 20062006
AN - SCOPUS:77649273915
VL - 23
SP - 359
EP - 366
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
IS - 3
ER -