PDF(Pubmed)
Abstract：
Uterine clear cell carcinoma (CCC) consists of either pure clear cell histology but can also display other histological components (mixed uterine CCCs). In this study, the molecular and immunohistochemical background of pure and mixed uterine CCC was compared. Secondly, it was evaluated whether histological classification and molecular background affected clinical outcome.
A retrospective multicenter study was performed comparing pure uterine CCCs (n = 22) and mixed uterine CCCs (n = 21). Targeted next-generation sequencing using a 12-gene targeted panel classified cases as polymerase-ε (POLE) mutated, microsatellite instable (MSI), TP53 wildtype or TP53 mutated. Immunohistochemistry was performed for estrogen receptor, progesterone receptor, L1 cell adhesion molecule, MSH6, and PMS2.
The following molecular subgroups were identified for pure and mixed uterine CCCs, respectively: POLE mutated 0% (0/18) and 6% (1/18); MSI in 6% (1/18) and 50% (9/18); TP53 wildtype in 56% (10/18) and 22% (4/18); TP53 mutated in 39% (7/18) and 22% (4/18) (p = 0.013). Patients with mixed CCCs had improved outcome compared to patients with pure CCCs. Frequent TP53 mutations were found in pure CCCs and frequent MSI in mixed CCCs, associated with clinical outcome.
Pure and mixed uterine CCCs are two entities with different clinical outcomes, which could be explained by different molecular backgrounds. These results underline the relevance of both morphological and molecular evaluation, and may assist in tailoring treatment.
A retrospective multicenter study was performed comparing pure uterine CCCs (n = 22) and mixed uterine CCCs (n = 21). Targeted next-generation sequencing using a 12-gene targeted panel classified cases as polymerase-ε (POLE) mutated, microsatellite instable (MSI), TP53 wildtype or TP53 mutated. Immunohistochemistry was performed for estrogen receptor, progesterone receptor, L1 cell adhesion molecule, MSH6, and PMS2.
The following molecular subgroups were identified for pure and mixed uterine CCCs, respectively: POLE mutated 0% (0/18) and 6% (1/18); MSI in 6% (1/18) and 50% (9/18); TP53 wildtype in 56% (10/18) and 22% (4/18); TP53 mutated in 39% (7/18) and 22% (4/18) (p = 0.013). Patients with mixed CCCs had improved outcome compared to patients with pure CCCs. Frequent TP53 mutations were found in pure CCCs and frequent MSI in mixed CCCs, associated with clinical outcome.
Pure and mixed uterine CCCs are two entities with different clinical outcomes, which could be explained by different molecular backgrounds. These results underline the relevance of both morphological and molecular evaluation, and may assist in tailoring treatment.
摘要：
背景：子宫透明细胞癌（CCC）由纯透明细胞组织学组成，但也可以显示其他组织学成分（混合子宫CCCs）。在这项研究中,比较了纯子宫和混合子宫CCC的分子和免疫组织化学背景。其次,我们评估了组织学分类和分子背景是否影响临床结局.
方法：进行了一项回顾性多中心研究，比较了纯子宫CCCs（n=22）和混合子宫CCCs（n=21）。使用12个基因靶向小组的靶向下一代测序将病例分类为聚合酶-ε（POLE）突变，微卫星不稳定(MSI)，TP53野生型或TP53突变。对雌激素受体进行免疫组织化学，孕激素受体,L1细胞粘附分子,MSH6和PMS2。
结果：确定了纯和混合子宫CCCs的以下分子亚群，分别为:POLE突变0%(0/18)和6%(1/18);MSI突变6%(1/18)和50%(9/18);TP53野生型突变56%(10/18)和22%(4/18);TP53突变39%(7/18)和22%(4/18)(p=0.013)。与纯CC患者相比，混合CC患者的预后有所改善。在纯CC中发现频繁的TP53突变，在混合CC中发现频繁的MSI，与临床结果相关。
结论：纯子宫CCCs和混合子宫CCCs是两种具有不同临床结局的实体，这可以用不同的分子背景来解释。这些结果强调了形态学和分子评估的相关性，并可能有助于定制治疗。
方法：进行了一项回顾性多中心研究，比较了纯子宫CCCs（n=22）和混合子宫CCCs（n=21）。使用12个基因靶向小组的靶向下一代测序将病例分类为聚合酶-ε（POLE）突变，微卫星不稳定(MSI)，TP53野生型或TP53突变。对雌激素受体进行免疫组织化学，孕激素受体,L1细胞粘附分子,MSH6和PMS2。
结果：确定了纯和混合子宫CCCs的以下分子亚群，分别为:POLE突变0%(0/18)和6%(1/18);MSI突变6%(1/18)和50%(9/18);TP53野生型突变56%(10/18)和22%(4/18);TP53突变39%(7/18)和22%(4/18)(p=0.013)。与纯CC患者相比，混合CC患者的预后有所改善。在纯CC中发现频繁的TP53突变，在混合CC中发现频繁的MSI，与临床结果相关。
结论：纯子宫CCCs和混合子宫CCCs是两种具有不同临床结局的实体，这可以用不同的分子背景来解释。这些结果强调了形态学和分子评估的相关性，并可能有助于定制治疗。
