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双侧输卵管浆液性上皮内瘤的单克隆起源证据。

Evidence of a Monoclonal Origin for Bilateral Serous Tubal Intraepithelial Neoplasia.

机构信息

Department of Pathology, Maine Medical Center, Portland, Maine (E.E.M.) Department of Pathology, Duke University Medical Center, Durham, North Carolina (K.C.S.) PlexSeq Diagnostics, Cleveland, Ohio (A.M., F.C.) Department of Pathology, Division of Women's and Perinatal Pathology, Brigham; and Women's Hospital, Boston, Massachusetts (T.R.S., C.P.C.) Department of Pathology, Stanford University Medical Center, Stanford, California (B.E.H.).

出版信息

Int J Gynecol Pathol. 2019 Sep;38(5):443-448. doi: 10.1097/PGP.0000000000000534.

DOI:10.1097/PGP.0000000000000534
PMID:29901519
Abstract

Serous tubal intraepithelial carcinoma (STIC) is found in 10% to 60% of cases of tuboovarian high-grade serous carcinoma (HGSC) and is presumed to be the site of origin, linking many HGSCs to the fallopian tube. Bilateral STIC is present in ∼20% of cases. Because clonal Tp53 mutations are a defining feature of HGSC, including their associated STICs, we analyzed 4 cases of bilateral serous tubal intraepithelial neoplasia (STIN), including STIC and Tp53-mutated serous tubal intraepithelial lesions (STILs), associated with HGSC to determine whether they contained the same or different p53 mutations. Extracted DNA from STINs, concurrent HGSCs and control tissues was analyzed for mutations in all exons of Tp53. Sequencing was successful in 3 of the 4 cases, and an identical Tp53 mutation was detected in the HGSC and bilateral STINs in 2 of these 3 cases. One STIN was morphologically a STIL. These findings confirm that a subset of bilateral STINs share the same Tp53 mutation, implying that at least one of the STINs is an intraepithelial metastasis from either the contralateral STIN or HGSC. This study complements others addressing the multiple origins of STIN in the setting of existing HGSC. It further underscores the fact that potential overlap in biologic behavior between STILs and STICs as well as timing and direction of metastatic spread has yet to be resolved.

摘要

输卵管上皮内癌(STIC)见于 10%~60%的输卵管卵巢高级别浆液性癌(HGSC)病例中,被认为是起源部位,将许多 HGSC 与输卵管联系起来。双侧 STIC 见于约 20%的病例中。由于克隆性 Tp53 突变是 HGSC 的一个明确特征,包括其相关的 STIC,我们分析了 4 例双侧输卵管上皮内浆液性肿瘤(STIN),包括 STIC 和 Tp53 突变的输卵管上皮内病变(STIL),与 HGSC 相关,以确定它们是否含有相同或不同的 p53 突变。从 STIN、同时发生的 HGSC 和对照组织中提取的 DNA 进行 Tp53 所有外显子的突变分析。在这 4 例中有 3 例测序成功,其中 2 例在 HGSC 和双侧 STIN 中检测到相同的 Tp53 突变。有 1 例 STIN 在形态学上是 STIL。这些发现证实了一部分双侧 STIN 具有相同的 Tp53 突变,这意味着至少有一个 STIN 是来自对侧 STIN 或 HGSC 的上皮内转移。本研究补充了其他在现有 HGSC 背景下探讨 STIN 多种起源的研究。它进一步强调了 STIL 和 STIC 之间在生物学行为上的潜在重叠,以及转移扩散的时间和方向尚未得到解决。

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J Ovarian Res. 2023 Nov 20;16(1):218. doi: 10.1186/s13048-023-01307-x.
2
Mechanisms of High-Grade Serous Carcinogenesis in the Fallopian Tube and Ovary: Current Hypotheses, Etiologic Factors, and Molecular Alterations.输卵管和卵巢高级别浆液性癌发生的机制:当前假说、病因因素和分子改变。
Int J Mol Sci. 2021 Apr 23;22(9):4409. doi: 10.3390/ijms22094409.
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Back to the Future? The Fallopian Tube, Precursor Escape and a Dualistic Model of High-Grade Serous Carcinogenesis.
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Cancers (Basel). 2018 Nov 28;10(12):468. doi: 10.3390/cancers10120468.