Prognostic Integrated Image-Based Immune and Molecular Profiling in Early-Stage Endometrial Cancer

Nanda Horeweg, Marco de Bruyn, Remi A Nout, Ellen Stelloo, Katarzyna Z Kedzierska, Alicia León-Castillo, Annechien Plat, Kirsten D Mertz, Michelle Osse, Ina M Jürgenliemk-Schulz, Ludy C Lutgens, Jan J Jobsen, Elzbieta M van der Steen-Banasik, Vincent T H B M Smit, Carien L Creutzberg, Tjalling Bosse, Hans W Nijman, Viktor H Koelzer, David N Church*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

18 Citaten (Scopus)
93 Downloads (Pure)


Optimum risk stratification in early-stage endometrial cancer combines clinicopathologic factors and the molecular endometrial cancer classification defined by The Cancer Genome Atlas (TCGA). It is unclear whether analysis of intratumoral immune infiltrate improves this. We developed a machine-learning, image-based algorithm to quantify density of CD8(+) and CD103(+) immune cells in tumor epithelium and stroma in 695 stage I endometrioid endometrial cancers from the PORTEC-1 and -2 trials. The relationship between immune cell density and clinicopathologic/molecular factors was analyzed by hierarchical clustering and multiple regression. The prognostic value of immune infiltrate by cell type and location was analyzed by univariable and multivariable Cox regression, incorporating the molecular endometrial cancer classification. Tumor-infiltrating immune cell density varied substantially between cases, and more modestly by immune cell type and location. Clustering revealed three groups with high, intermediate, and low densities, with highly significant variation in the proportion of molecular endometrial cancer subgroups between them. Univariable analysis revealed intraepithelial CD8(+) cell density as the strongest predictor of endometrial cancer recurrence; multivariable analysis confirmed this was independent of pathologic factors and molecular subgroup. Exploratory analysis suggested this association was not uniform across molecular subgroups, but greatest in tumors with mutant p53 and absent in DNA mismatch repair-deficient cancers. Thus, this work identified that quantification of intraepithelial CD8thorn cells improved upon the prognostic utility of the molecular endometrial cancer classification in early-stage endometrial cancer.

Originele taal-2English
Pagina's (van-tot)1508-1519
Aantal pagina's12
TijdschriftCancer immunology research
Nummer van het tijdschrift12
Vroegere onlinedatum30-sep-2020
StatusPublished - 1-dec-2020

Citeer dit