骨肿瘤端粒长度变化与相关蛋白表达的关系

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

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 get insight into the molecular features in tumorigenesis of bone tumors, the changes in telomerie length, expression of binding proteins and telomemse 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 hybridization（Telo-FISH）, and the expression ofTRF1, POTI, 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 ofchondrosarcomas, 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 TRF1 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 telomerie length in bone tumors was negatively with the expression of telomere binding protein TRF 1 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.