Immunohistochemical Evaluation of Potential Biomarkers for Targeted Intraoperative Fluorescence Imaging in Endometriosis
Towards Optimizing Surgical Treatment
Fokkedien H.M.P. Tummers (Leiden University Medical Center)
Rozemarijn de Koning (Leiden University Medical Center)
Maria K. Bazelmans (Leiden University Medical Center)
Frank Willem Jansen (TU Delft - Mechanical Engineering, Leiden University Medical Center)
Mathijs D. Blikkendaal (Haaglanden Medical Center, Reinier de Graaf Gasthuis)
Ronald L.P. van Vlierberghe (Leiden University Medical Center)
Alexander L. Vahrmeijer (TU Delft - Mechanical Engineering, Leiden University Medical Center)
Hans Marten Hazelbag (Haaglanden Medical Center)
Peter J.K. Kuppen (Leiden University Medical Center)
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Abstract
Surgical intervention for endometriosis is an important treatment modality, yet incomplete resection resulting from poor visibility of affected tissue and consequently recurrence of disease remains a prevalent challenge. Intra-operative visualization of endometriosis, enabling fluorescence-guided surgery (FGS), could help to optimize surgical treatment. A biomarker, upregulated in endometriosis compared to adjacent tissue, is required to use as a target for FGS. Immunohistochemistry was used to evaluate protein expression of a selection of previously identified potential biomarkers. Ten biomarkers were stained in a large cohort of 84 tissues, both deep and peritoneal endometriosis and tissue without endometriosis, all from patients with confirmed endometriosis. MMP11 and VCAN showed the largest upregulation in endometriosis compared to adjacent tissue and showed a membranous or extracellular staining pattern. MMP11 is a promising target for glandular and stromal visualization, VCAN for stromal visualization only. For both biomarkers, upregulation was high in both peritoneal and deep endometriosis and for patients with and without hormonal medication. Other stained biomarkers showed non-beneficial characteristics based on staining pattern or upregulation. Analysis of all endometriosis samples showed that combined glandular and stromal targeting is expected to result in optimal visualization of endometriosis. Further research is needed to determine whether targeting one biomarker is sufficient for this goal, or if dual targeting is necessary. Development of clinical tracers for VCAN and MMP11 is necessary.
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