Endometrial carcinoma and immune escape: prognostic relevance of HLA class I loss in NSMP subtype

Marco Grillini ^1,2, Jacopo Lenzi ³, Claudio Ceccarelli ²

¹Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
²Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
³Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
⁴Department of Pharmacy and Biotechnology (FaBit), University of Bologna, Bologna, Italy.
⁵Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁶University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.
⁷Division of Oncologic Gynecology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁸Addarii Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁹Laboratory of Translational Research, Arcispedale Santa Maria Nuova, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
¹⁰Department of Biopathology, Institut Bergonié, Bordeaux, France.
¹¹Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
¹²Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.

⁰Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Histopathology +

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August 12, 2025

View abstract on PubMed

Summary

Loss of human leukocyte antigen class I (HLA-I) in endometrial cancer (EC) is linked to aggressive features, particularly in the no specific molecular profile (NSMP) subtype. This finding may guide risk stratification and treatment for NSMP EC patients.

Area Of Science

Oncology
Immunology
Pathology

Background

Endometrial carcinoma (EC) exhibits diverse molecular subtypes.
Human leukocyte antigen class I (HLA-I) expression is crucial for anti-tumour immunity.
The prognostic significance of HLA-I in EC, especially the no specific molecular profile (NSMP) subtype, requires further elucidation.

Purpose Of The Study

To characterize HLA-I expression across molecularly defined EC subtypes.
To investigate the association of HLA-I expression with clinicopathologic features and immune phenotypes.
To evaluate the prognostic impact of HLA-I expression in EC, with a focus on the NSMP subtype.

Main Methods

Immunohistochemistry was used to assess HLA-I expression in 208 ECs.
ECs were classified into POLE-mutated, MMR-deficient (MMRd), p53-abnormal (p53abn), and NSMP subtypes.
Clinicopathologic data, spatial cancer-immune phenotypes, and patient survival were analyzed.

Main Results

HLA-I loss was observed in 31% of EC cases and associated with adverse features (high-grade, LVSI, necrosis).
HLA-I loss significantly correlated with worse disease-free survival specifically in NSMP tumours (P < 0.001).
Multivariate analysis identified HLA-I loss as an independent prognostic factor in early-stage NSMP ECs.

Conclusions

Loss of HLA-I identifies a biologically aggressive subgroup within NSMP ECs.
HLA-I expression assessment can refine risk stratification for NSMP ECs.
Identifying HLA-I loss may guide intensified surveillance and immunomodulatory treatment strategies.

Keywords:

HLA‐I endometrial carcinoma histopathological parameters immune phenotype molecular classification risk stratification tumour microenvironment