Prognostic significance of CK7, CK20, and CDX2 expression in small intestinal adenocarcinoma.
15 affiliations
- 1Laboratory of Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam UMC and University of Amsterdam, Amsterdam, The Netherlands.
- 2Oncode Institute, Utrecht, The Netherlands.
- 3Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
- 4Departments of Medical Oncology, Amsterdam UMC, Amsterdam, The Netherlands.
- 5Departments of Gastroenterology, Amsterdam UMC, Amsterdam, The Netherlands.
- 6Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
- 7Departments of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.
- 8Departments of Surgery, Amsterdam UMC, Amsterdam, The Netherlands.
- 9Department of Pathology, OLVG, Amsterdam, The Netherlands.
- 10Netherlands Cancer Institute, Department of Gastrointestinal Oncology, Amsterdam, The Netherlands.
- 11Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands.
- 12Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.
- 13Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
- 14Department of Internal Medicine, Meander Medical Center, Amersfoort, The Netherlands.
- 15Department of Internal Medicine, Flevo Hospital, Almere, The Netherlands.
Abstract
Background
Small intestinal adenocarcinoma (SIA) is a rare gastrointestinal malignancy for which prognostic biomarkers remain poorly defined. Immunohistochemical markers cytokeratin 7 (CK7), cytokeratin 20 (CK20), and caudal-type homeobox transcription factor 2 (CDX2) are diagnostic markers that are prognostic in other intestinal cancers, but their prognostic significance in SIA has not been studied before.Patients and methods
This nationwide, retrospective, population-based cohort study used data from the Netherlands Cancer Registry and the Dutch pathology database. Patients diagnosed with primary SIA between 1999 and 2019 and with registered CK7, CK20, or CDX2 expression levels were included. Overall survival (OS) was analyzed using Kaplan-Meier curves and multivariable Cox regression models adjusted for age, sex, stage, tumor location, and treatment. The findings were validated in a detailed cohort of 128 SIA patients.Results
Of 2697 patients diagnosed with SIA, expression data were available for 691 patients. CK7 positivity was associated with more proximal, advanced, and microsatellite stable tumors. CK7-negative, CK20-positive, and CDX2-positive tumors demonstrated significantly improved OS (all P ≤ 0.002). In multivariable analysis, lack of CK20 and CDX2 expression were independent predictors of poorer survival [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.02-1.83 and HR 1.51, 95% CI 1.06-2.17, respectively]. Combined expression profiles identified distinct prognostic subgroups, which were confirmed in the validation cohort.Conclusion
CK20 and CDX2 expression are independent prognostic biomarkers in SIA, regardless of primary tumor location. Their assessment may improve risk stratification and refine disease classification, bridging diagnostic and prognostic utility in this rare cancer type.
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BibTeX
@article{schafrat2026prognostic,
title = {{Prognostic significance of CK7, CK20, and CDX2 expression in small intestinal adenocarcinoma.}},
author = {P J M Schafrat and J D G Linssen and T R de Back and L E Nijman and M C S van der Heijden and N C T van Grieken and G Kazemier and P Drillenburg and M Chalabi and F N van Erning and I H J T de Hingh and R S A Goedegebuure and D W Sommeijer and A Farina Sarasqueta and L Vermeulen},
journal = {ESMO gastrointestinal oncology},
year = {2026},
month = jun,
doi = {10.1016/j.esmogo.2026.100346},
url = {https://europepmc.org/article/MED/42948310},
note = {CC BY},
}
RIS
TY - JOUR
TI - Prognostic significance of CK7, CK20, and CDX2 expression in small intestinal adenocarcinoma.
AU - P J M Schafrat
AU - J D G Linssen
AU - T R de Back
AU - L E Nijman
AU - M C S van der Heijden
AU - N C T van Grieken
AU - G Kazemier
AU - P Drillenburg
AU - M Chalabi
AU - F N van Erning
AU - I H J T de Hingh
AU - R S A Goedegebuure
AU - D W Sommeijer
AU - A Farina Sarasqueta
AU - L Vermeulen
PY - 2026
DA - 2026/06/18
JO - ESMO gastrointestinal oncology
DO - 10.1016/j.esmogo.2026.100346
UR - https://europepmc.org/article/MED/42948310
AB - Background Small intestinal adenocarcinoma (SIA) is a rare gastrointestinal malignancy for which prognostic biomarkers remain poorly defined. Immunohistochemical markers cytokeratin 7 (CK7), cytokeratin 20 (CK20), and caudal-type homeobox transcription factor 2 (CDX2) are diagnostic markers that are prognostic in other intestinal cancers, but their prognostic significance in SIA has not been studied before.Patients and methods This nationwide, retrospective, population-based cohort study used data from the Netherlands Cancer Registry and the Dutch pathology database. Patients diagnosed with primary SIA between 1999 and 2019 and with registered CK7, CK20, or CDX2 expression levels were included. Overall survival (OS) was analyzed using Kaplan-Meier curves and multivariable Cox regression models adjusted for age, sex, stage, tumor location, and treatment. The findings were validated in a detailed cohort of 128 SIA patients.Results Of 2697 patients diagnosed with SIA, expression data were available for 691 patients. CK7 positivity was associated with more proximal, advanced, and microsatellite stable tumors. CK7-negative, CK20-positive, and CDX2-positive tumors demonstrated significantly improved OS (all P ≤ 0.002). In multivariable analysis, lack of CK20 and CDX2 expression were independent predictors of poorer survival [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.02-1.83 and HR 1.51, 95% CI 1.06-2.17, respectively]. Combined expression profiles identified distinct prognostic subgroups, which were confirmed in the validation cohort.Conclusion CK20 and CDX2 expression are independent prognostic biomarkers in SIA, regardless of primary tumor location. Their assessment may improve risk stratification and refine disease classification, bridging diagnostic and prognostic utility in this rare cancer type.
SN - 2949-8198
ER -