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目的:研究骨肿瘤端粒长度变化与端粒结合蛋白即端粒重复结合因子1(TRF1)和端粒保护因子(POT1),端粒酶催化亚单位(hTERT),肿瘤相关基因P53、c-myc表达的关系,以了解骨肿瘤的分子特征。方法:采用免疫组织化学、端粒定量荧光原位杂交(Telo-FISH)和原位杂交检测了20例骨肉瘤、25例软骨肉瘤、14例骨的纤维结构不良中端粒长度、TRF1、POT1、hTERT、P53、c-myc的表达情况,并进行统计分析。结果:20例骨肉瘤平均长度为0.31,25例软骨肉瘤为0.41,14例骨的纤维结构不良为0.52。统计显示三者间端粒长度有显著差异(P<0.05)。骨肉瘤和软骨肉瘤TRF1、POT1阳性率均显著低于骨纤维结构不良(P<0.05)。而骨肉瘤和软骨肉瘤hTERT基因表达显著高于骨纤维结构不良(P<0.05)。骨肉瘤、软骨肉瘤P53、c-myc阳性率高于骨纤维结构不良(P<0.05)。统计分析骨肿瘤端粒长度变化与端粒结合蛋白TRF1、POT1的表达呈负相关性,与端粒酶hTERT基因表达、与P53蛋白核聚积,以及c-myc癌基因表达呈正相关性。结论:骨肿瘤端粒长度与恶性表型有关、端粒短缩与肿瘤基因突变相关。
OBJECTIVE: To study the correlation between telomere length changes and telomere binding protein TRF1, POT1, hTERT, P53, c- myc expression in order to understand the molecular characteristics of bone tumors. Methods: The telomere length of 20 cases of osteosarcoma, 25 cases of chondrosarcoma and 14 cases of fibrous dysplasia were detected by immunohistochemistry, Telo-FISH and in situ hybridization. The expressions of TRF1, POT1 , HTERT, P53, c-myc expression, and statistical analysis. Results: The average length of osteosarcoma in 20 cases was 0.31, that in chondrosarcoma was 0.41 in 5 cases, and that in 14 cases was 0.52. Statistics show that the telomere length between the three significant differences (P <0.05). The positive rates of TRF1 and POT1 in osteosarcoma and chondrosarcoma were significantly lower than those in skeletal fiber (P <0.05). The expression of hTERT gene in osteosarcoma and chondrosarcoma was significantly higher than that in skeletal fiber (P <0.05). The positive rates of P53 and c-myc in osteosarcoma and chondrosarcoma were higher than those in fibrous tissue (P <0.05). Statistical analysis showed that there was a negative correlation between telomere length changes and TRF1 and POT1 expression, which was positively correlated with telomerase hTERT gene expression, P53 protein nuclear accumulation and c-myc oncogene expression. Conclusion: The telomere length of bone tumor is related to malignant phenotype. Telomere shortening is associated with tumor gene mutation.