Correlation of microscopic tumor extension with tumor microenvironment in esophageal cancer patients

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Objective: In the era of image-guided adaptive radiotherapy, definition of the clinical target volume (CTV) is a challenge in various solid tumors, including esophageal cancer (EC). Many tumor microenvironmental factors, e.g., tumor cell proliferation or cancer stem cells, are hypothesized to be involved in microscopic tumor extension (MTE). Therefore, this study assessed the expression of FAK, ILK, CD44, HIF-1α, and Ki67 in EC patients after neoadjuvant radiochemotherapy followed by tumor resection (NRCHT+R) and correlated these markers with the MTE. Methods: Formalin-fixed paraffin-embedded tumor resection specimens of ten EC patients were analyzed using multiplex immunofluorescence staining. Since gold fiducial markers had been endoscopically implanted at the proximal and distal tumor borders prior to NRCHT+R, correlation of the markers with the MTE was feasible. Results: In tumor resection specimens of EC patients, the overall percentages of FAK+, CD44+, HIF-1α+, and Ki67+ cells were higher in tumor nests than in the tumor stroma, with the outcome for Ki67+ cells reaching statistical significance (p < 0.001). Conversely, expression of ILK+ cells was higher in tumor stroma, albeit not statistically significantly. In three patients, MTE beyond the fiducial markers was found, reaching up to 31 mm. Conclusion: Our findings indicate that the overall expression of FAK, HIF-1α, Ki67, and CD44 was higher in tumor nests, whereas that of ILK was higher in tumor stroma. Differences in the TME between patients with residual tumor cells in the original CTV compared to those without were not found. Thus, there is insufficient evidence that the TME influences the required CTV margin on an individual patient basis. Trial registration number and date: BO-EK-148042017 and BO-EK-177042022 on 20.06.2022, DRKS00011886, https://drks.de/search/de/trial/DRKS00011886.

Details

Original languageEnglish
Pages (from-to)595-604
Number of pages10
JournalStrahlentherapie und Onkologie
Volume200
Issue number7
Publication statusPublished - Jul 2024
Peer-reviewedYes

External IDs

PubMed 38727811
ORCID /0000-0002-7017-3738/work/162845809

Keywords

Sustainable Development Goals

Keywords

  • Clinical Target Volume, Hypoxia, Immunohistochemical analysis, Multiparametric analysis, Proliferation, Tumor stem cells, Hyaluronan Receptors/analysis, Fiducial Markers, Humans, Middle Aged, Tumor Microenvironment, Male, Radiotherapy, Image-Guided, Esophageal Neoplasms/pathology, Biomarkers, Tumor/analysis, Focal Adhesion Kinase 1/metabolism, Female, Neoadjuvant Therapy, Aged, Hypoxia-Inducible Factor 1, alpha Subunit/metabolism, Ki-67 Antigen/analysis