Shortened telomeres in serous tubal intraepithelial carcinoma: an early event in ovarian high-grade serous carcinogenesis.
Shortened telomeres in serous tubal intraepithelial carcinoma: an early event in ovarian high-grade serous carcinogenesis.
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DOI：
10.1097/pas.0b013e3181dcede7
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Shih IeM
中科院分区：
文献类型：
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作者：
Kuhn E;Meeker A;Wang TL;Sehdev AS;Kurman RJ;Shih IeM
短端粒是人类癌症的主要遗传表现之一，因为它们已被证明在诱导染色体不稳定性和促进肿瘤进展方面发挥重要作用。本研究的目的是确定浆液性输卵管上皮内癌（STIC）是否发生端粒长度的变化，STIC是“卵巢”高级别浆液性癌（HGSC）的假定前体。通过进行p53免疫荧光以辅助识别STIC和端粒特异性FISH，分析来自15例同时但离散HGSC患者的22个STIC在福尔马林固定的石蜡包埋切片上的端粒长度。使用正常输卵管上皮和基质细胞作为对照，将STIC中的端粒长度（短、长或无变化）与HGSC进行比较。我们发现STIC具有最短的端粒，因为22个STIC中有18个（82%）具有短端粒，而与正常外观的输卵管上皮相比，只有2个（9%）没有变化，2个（9%）具有长端粒。相比之下，在12对HGSC和STIC中，6个HGSC显示端粒长度增加，1个显示长度减少，5个与其匹配的STIC相比没有显示任何变化，尽管如STIC，大多数HGSC的端粒比相关的正常输卵管上皮细胞短。正常输卵管上皮细胞与STICs、STICs与HGSC的端粒长度差异有统计学意义（P<0.05）。总之，短端粒的发现，这已被证明是最早的分子变化在致癌作用，在绝大多数STIC提供了进一步的支持的建议，STIC是HGSC的前体，并开辟了新的研究领域，阐明卵巢高级别浆液性癌的早期事件。
Short telomeres are one of the main genetic manifestations in human cancer, as they have been shown to play an important role in inducing chromosomal instability and in contributing to tumor progression. The purpose of this study was to determine if changes in telomere length occur in serous tubal intraepithelial carcinoma (STIC), the putative precursor of “ovarian” high-grade serous carcinoma (HGSC). Twenty-two STICs from 15 patients with concurrent but discrete HGSCs were analyzed for telomere length on formalin-fixed, paraffin-embedded sections by conducting p53 immunofluorescence to assist in identifying STICs and telomere-specific FISH. Telomere length (short, long, or no change) in STICs was compared with HGSCs using normal fallopian tube epithelium and stromal cells as controls. We found that STICs had the shortest telomeres, as 18 (82%) of 22 STICs had short telomeres, whereas only 2 (9%) showed no change and 2 (9%) had long telomeres compared with the normal-looking tubal epithelium. In contrast, among 12 paired HGSCs and STICs, 6 HGSCs showed an increase in telomere length, one showed a decrease in length and 5 did not show any change when compared with their matched STICs, although, such as STICs, the majority of HGSCs had shorter telomeres than the associated normal tubal epithelial cells. These differences in telomere length between normal tubal epithelial cells and STICs, and between STICs and HGSCs were statisticaly significant (P<0.05). In conclusion, the finding of short telomeres, which have been shown to be one of the earliest molecular changes in carcinogenesis, in a vast majority of STICs provides further support to the proposal that STICs are precursors of HGSC and opens new areas of research in elucidating the early events of ovarian high-grade serous carcinogenesis.