No specific molecular profile (NSMP) endometrial cancer

What is measured: a diagnosis by exclusion within the ProMisE and WHO 2020 classification. How: POLE exonuclease domain sequencing negative, mismatch repair immunohistochemistry (MLH1, PMS2, MSH2, MSH6) intact, p53 immunohistochemistry wild-type pattern. About half of endometrial carcinomas fall here, with an intermediate and heterogeneous outcome, so the group is refined by oestrogen receptor expression (ER-negative NSMP behaves like p53-abnormal disease), grade, L1CAM expression, lymphovascular space invasion, depth of myometrial invasion and CTNNB1 exon 3 mutation (higher recurrence in otherwise low-grade tumours). PTEN, PIK3CA and ARID1A mutations are frequent. What a result changes: adjuvant treatment follows the ESGO/ESTRO/ESP molecular risk groups (vaginal brachytherapy for intermediate risk, chemoradiation for high risk); advanced ER-positive NSMP disease is a candidate for endocrine therapy (progestins, aromatase inhibitors, with CDK4/6 inhibitors in trials); the RAINBO NSMP-ORANGE trial tests endocrine therapy in place of chemotherapy after radiotherapy. Where it matters: the NSMP endometrial page.