From integrative diagnostics to personalised management: a framework combining molecular and spatial immune profiling...

Endometrial carcinoma (EC) of the No Specific Molecular Profile (NSMP) subtype, the largest molecular category, exhibits marked clinical heterogeneity that challenges morphology-based risk assessment. Two complementary biomarker categories have demonstrated independent prognostic value: protein-level markers (L1CAM, oestrogen receptor [ER], and progesterone receptor [PR]) detectable by routine immunohistochemistry and spatially resolved cancer-immune phenotypes (SCIs) that characterize the tumour immune microenvironment. This review synthesises evidence for both, highlighting that they are often considered in isolation. We argue that their systematic integration is essential for a more precise diagnostic framework. We articulate the biological rationale and propose a testable "dual-risk" hypothesis, whereby combined molecular and immune profiling could identify extreme-risk populations. Realising this integrative model requires overcoming standardisation hurdles, but it represents a critical step towards predictive, functionally informed stratification to guide personalised adjuvant therapy decisions, including intensification and de-escalation. We emphasise that this framework remains a testable hypothesis requiring prospective validation before clinical application.