RESUMEN
OBJECTIVE: To explore the significance in the change of telomere length in mesenchymal sarcomas, through analyzing telomere length and expression of its associated proteins, including TRF1, POT1, hTERT, P53 and c-myc. METHODS: The telomere length in 20 cases of osteosarcomas, 25 of chondrosarcomas, 19 of rhabdomyosarcomas, 26 of liposarcomas was measured by telomere fluorescence in situ hybridization (Telo-FISH), and the expression of TRF1, POT1, hTERT, p53 or c-myc was analyzed by immunohistochemistry, respectively. RESULTS: The telomere length in osteosarcomas was significantly shorter than that of either chondrosarcomas or liposarcomas (P<0.05). Similarly, the telomere length of rhabdomyosarcoma was shorter than that of chondrosarcoma (P<0.05). Meanwhile, telomere shortening was positively correlated with down expression of telomere binding proteins TRF1 and POT1 (P<0.05), but trends were detected more frequently in positive expression of hTERT (P<0.05) and in nuclear accumulation of P53 or expression of c-myc. With advancing in histological grading, telomere length was shortened markedly in chondrosarcomas, especially in liposarcomas (P<0.05). CONCLUSION: The shortening of telomere could prevail in mesenchymal sarcoma and reflect the malignant potential. Telomere attrition usually correlated with down expression of POT1, TRF1 and with increased levels of hTERT, P53 and c-myc.
Asunto(s)
Neoplasias Óseas/genética , Osteosarcoma/genética , Proteínas de Unión a Telómeros/metabolismo , Telómero/ultraestructura , Adulto , Neoplasias Óseas/metabolismo , Condrosarcoma/genética , Condrosarcoma/metabolismo , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Liposarcoma/genética , Liposarcoma/metabolismo , Masculino , Persona de Mediana Edad , Osteosarcoma/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Rabdomiosarcoma/genética , Rabdomiosarcoma/metabolismo , Complejo Shelterina , Telomerasa/genética , Telomerasa/metabolismo , Proteínas de Unión a Telómeros/genética , Proteína 1 de Unión a Repeticiones Teloméricas/genética , Proteína 1 de Unión a Repeticiones Teloméricas/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: To evaluate the expression of TEIF protein in human tumors of soft tissue and its significance. METHODS: Anti-TEIF polyclonal antibody was generated by immunization of E.coli expressed His-TEIF protein. The expression of TEIF in 166 cases of sarcomas and 28 case benign tumors or tumor-like lesions of soft tissue arranged in tissue chip was analyzed by immunohistochemistry. RESULTS: Polyclonal antibody obtained from immunized rabbit was verified in Western blot to prove its specific reactivity with native TEIF protein. The immunohistochemical staining of TEIF showed that about 58% (97/166) of sarcomas were positive and significantly different from that of benign tumors or tumor-like lesions (11%, 3/28). The positive staining was predominantly in synovial sarcoma 94% (16/17), primitive neuroectodermal tumor (PNET) 91% (21/23), both of which were significantly higher than 43% (6/14) of dermatofibrosarcoma protuberans, 38% (6/16) of myxofibrosarcoma, 36% (8/22) of malignant peripheral nerve sheath tumor, 32% (6/19) of liposarcoma, (P < 0.05, respectively), but not higher than 75% (15/20) of malignant fibrous histiocytoma, 70% (7/10) of rhabdomyosarcoma or 64% (9/14) of leiomyosarcoma. Meanwhile, strong positive staining of TEIF (>or= 2+) was frequently observed in PNET (83%, 19/23) and synovial sarcoma (76%, 13/17). With respect to FNCLCC grading, 19 cases of grade I sarcoma TEIF was 32% (6/19) and strong positive was 11% (2/19), 44 cases of grade II sarcoma was 48% (21/44) and 32% (14/44), and 70 of grade III was 84% (59/70) and 70% (49/70). The rate of either positive or strong positive in grade III sarcoma was significantly different from that of either grade I or II (P < 0.05), but no difference between the latter two groups (P > 0.05). CONCLUSIONS: TEIF protein could be detected in large part of soft tissue sarcomas, and it not only over-expressed in most of PNET, synovial sarcomas, but also correlated with histological grading.