Abstract:
Endometrial carcinoma (EC) is the most frequent gynecological cancer, with an increasing incidence and mortality in recent times. The last decade has represented a true revolution with the development of the integrated histo-molecular classification of EC, which allows for the stratification of patients with morphologically indistinguishable disease into groups with different prognoses. Particularly, the POLE-mutated subgroup exhibits outstanding survival. Nevertheless, the indiscriminate application of molecular classification appears premature. Its prognostic significance has been proven mainly in endometrioid EC, the most common histotype, but it has yet to be convincingly confirmed in the other minor histotypes, which indeed account for a relevant proportion of EC mortality. Moreover, its daily use both requires a mindful pathologist who is able to correctly evaluate and unambiguously report immunohistochemical staining used as a surrogated diagnostic tool and is hampered by the unavailability of POLE mutation analysis. Further molecular characterization of ECs is needed to allow for the identification of better-tailored therapies in different settings, as well as the safe avoidance of surgery for fertility preservation. Hopefully, the numerous ongoing clinical trials in the adjuvant and metastatic settings of EC will likely produce evidence to refine the histo-molecular classification and therapeutic guidelines. Our review aims to retrace the origin and evolution of the molecular classification for EC, reveal its strengths and limitations, show clinical relevance, and uncover the desired future developments.
摘要:
子宫内膜癌(EC)是最常见的妇科肿瘤,近年来发病率和死亡率不断上升。在过去的十年中,随着EC的综合组织分子分类的发展,这允许将形态学上无法区分疾病的患者分层为具有不同预后的组。特别是,POLE突变的亚组表现出出色的存活率。然而,不分青红皂白地应用分子分类似乎为时过早。其预后意义已被证明主要在子宫内膜样EC,最常见的组织型,但是在其他次要的组织学类型中还没有令人信服的证实,这确实占了欧共体死亡率的相关比例。此外,它的日常使用都需要一位有正念的病理学家能够正确评估并明确报告用作替代诊断工具的免疫组织化学染色,并且由于POLE突变分析的不可用而受到阻碍。需要对ECs进行进一步的分子表征,以便在不同的环境中识别出更好的定制疗法。以及安全避免手术保存生育能力。希望,在EC的辅助和转移环境中正在进行的大量临床试验可能为完善组织分子分类和治疗指南提供证据.我们的综述旨在追溯EC分子分类的起源和演变,揭示其优势和局限性,显示临床相关性,揭示未来的发展方向。