Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MA 21231, USA.
Mod Pathol. 2011 Aug;24(8):1139-45. doi: 10.1038/modpathol.2011.67. Epub 2011 Apr 15.
Ovarian carcinoma is composed of a heterogeneous group of tumors with distinct clinico-pathological and molecular features. Alteration of telomerase activity has been reported in ovarian tumors but the pattern of telomere length in their specific histological subtypes has not been reported. In this study, we performed quantitative telomere fluorescence in situ hybridization on a total of 219 ovarian carcinomas including 106 high-grade serous carcinomas, 26 low-grade serous carcinomas, 56 clear cell carcinomas and 31 low-grade endometrioid carcinomas. The mean relative telomere length of carcinoma to stromal cells was calculated as a telomere index. This index was significantly higher in clear cell carcinoma compared with the other histologic types (P=0.007). Overall there was no association between the telomere index and mortality, but when stratified by histologic types, the hazard ratio for death among women with clear cell carcinoma with a telomere index >1 was significantly increased at 4.93 (95% CI 1.64-14.86, P=0.005) when compared with those with a telomere index ≤1. In conclusion, our results provide new evidence that telomere length significantly differs by histologic type in ovarian carcinoma. Specifically, clear cell carcinomas have longer mean relative telomere lengths compared with the other histologic types and longer telomeres in clear cell carcinoma are associated with increased mortality suggesting that aberrations in telomere length may have an important role in the development and progression of this neoplasm.
卵巢癌由一组具有不同临床病理和分子特征的肿瘤组成。已经报道了端粒酶活性在卵巢肿瘤中的改变,但它们特定组织学亚型中端粒长度的模式尚未报道。在这项研究中,我们对总共 219 例卵巢癌进行了定量端粒荧光原位杂交,包括 106 例高级别浆液性癌、26 例低级别浆液性癌、56 例透明细胞癌和 31 例低级别子宫内膜样癌。计算癌与基质细胞的相对端粒长度的平均值作为端粒指数。与其他组织学类型相比,透明细胞癌的端粒指数显著更高(P=0.007)。总体而言,端粒指数与死亡率之间没有关联,但按组织学类型分层时,端粒指数>1 的透明细胞癌患者的死亡风险比端粒指数≤1 的患者显著增加,危险比为 4.93(95%CI 1.64-14.86,P=0.005)。总之,我们的结果提供了新的证据,表明卵巢癌中端粒长度在组织学类型上有显著差异。具体来说,与其他组织学类型相比,透明细胞癌的平均相对端粒长度更长,透明细胞癌中较长的端粒与死亡率增加相关,这表明端粒长度的异常可能在这种肿瘤的发生和进展中起着重要作用。