骨肿瘤端粒长度变化与相关蛋白表达的关系

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。

Correlation of Telomere Length in Bone Tumors with the Expression of Associated Proteins

Objective:To get insight into the molecular features in tumorigenesis of bone tumors,the changes in telomeric length, expression of binding proteins and telomerase as well as tumor-associated gene p53 and c-myc were analyzed.Methods:The telomere length in 20 osteosarcomas,25 chondrosarcomas,14 fibrous dysplasia of bone were measured by telomere fluorescence in situ hybridiza- tion(Telo-FISH),and the expression ofTRF1,POT1,hTERT,p53 or c-myc was analyzed by immunohistochemistry.In situ hybridization was also used to detect expression of hTERT.Results:The average telomeri length in 20 cases of osteosarcomas were determined 0.31, 0.41 for 25 of ehondrosareomas,0.52 for 14 of fibrous dysplasia of bone.There was a significant difference in the three groups of tumors in statistics(P<0.05).The expression of YRF1 or POT1 in osteosarcoma or chondrosarcoma was markedly weaker than that in fibrous dysplasia of bone(P<0.05).In contrast,hTERT in osteosarcoma and chondrosarcoma was much stronger(P<0.05).The nuclear staining of P53 and expression ofc-myc were far more frequent in osteosarcoma and chondrosarcoma(P<0.05).In addition,the telomeric length in bone tumors was negatively with the expression of telomere binding protein TRF1 and POT1,but was positively correlated with ex- pression of hTERT,nuclear accumulation of P53 and c-myc staining.Conclusions:The telomitic length reflects the malignant phenotype and the shortening of telomere correlates with gene mutation of bone tumor.