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<p>Molecular classification distinguishing between four subtypes should be performed in all endometrial cancers including carcinosarcomas, as recommended by international guidelines and standards. About 30% of all endometrial cancers harbor mismatch repair deficiency (dMMR), 15–20% <i>TP53</i> mutations or abnormal p53 protein expression (p53<sub>abn</sub>), and 5–10% pathogenic variants of polymerase&#xa0;E (<i>POLE</i> mutations; POLE<sub>mut</sub> tumors). The remaining 40–50% of cancers are designated NSMP (of no special molecular profile), since they lack these three molecular alterations. Prognosis is very favorable for POLE<sub>mut</sub> cancers, unfavorable for p53<sub>abn</sub> cancers, and dMMR cancers show an intermediate course. The NSMP cancers are separated into two prognostically relevant groups on the basis of estrogen receptor (ER) expression and histological grade: ER-positive low-grade tumors (grade&#xa0;1 or 2) with a favorable prognosis and ER-negative (&lt; 10% of tumor cells) or high grade (grade&#xa0;3) tumors with a poor prognosis. Complete analysis should be performed in every newly diagnosed and every recurrent endometrial cancer, preferentially on biopsy and curettage material, using a&#xa0;panel of immunohistochemical surrogate markers (MMR proteins, p53) and ER as well as POLE mutation analysis via real-time polymerase chain reaction (RT-PCR) or next-generation sequencing (NGS). The molecular type is predictive for the therapeutic response, particularly to immune checkpoint inhibition; its prognostic relevance is considered in the joint&#xa0;guidelines of the European Society of Gynecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) (ESGO-ESTRO-ESP guidelines); the German S3 guideline; and the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system.</p>

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Molekulare Klassifikation des Endometriumkarzinoms als Basis für Prognose- und Risikoeinschätzung sowie Therapie

  • 期刊论文

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  • 发表日期：

    2026年7月27日

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  • Sigurd F. Lax,
  • Lars-Christian Horn,
  • Clemens Tempfer

摘要

Molecular classification distinguishing between four subtypes should be performed in all endometrial cancers including carcinosarcomas, as recommended by international guidelines and standards. About 30% of all endometrial cancers harbor mismatch repair deficiency (dMMR), 15–20% TP53 mutations or abnormal p53 protein expression (p53abn), and 5–10% pathogenic variants of polymerase E (POLE mutations; POLEmut tumors). The remaining 40–50% of cancers are designated NSMP (of no special molecular profile), since they lack these three molecular alterations. Prognosis is very favorable for POLEmut cancers, unfavorable for p53abn cancers, and dMMR cancers show an intermediate course. The NSMP cancers are separated into two prognostically relevant groups on the basis of estrogen receptor (ER) expression and histological grade: ER-positive low-grade tumors (grade 1 or 2) with a favorable prognosis and ER-negative (< 10% of tumor cells) or high grade (grade 3) tumors with a poor prognosis. Complete analysis should be performed in every newly diagnosed and every recurrent endometrial cancer, preferentially on biopsy and curettage material, using a panel of immunohistochemical surrogate markers (MMR proteins, p53) and ER as well as POLE mutation analysis via real-time polymerase chain reaction (RT-PCR) or next-generation sequencing (NGS). The molecular type is predictive for the therapeutic response, particularly to immune checkpoint inhibition; its prognostic relevance is considered in the joint guidelines of the European Society of Gynecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) (ESGO-ESTRO-ESP guidelines); the German S3 guideline; and the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system.