Introduction/Background The strongest prognostic factor in epithelial ovarian cancer (EOC) is the completeness of surgery. During both surgical staging in apparent early stage disease and cytoreductive surgery in patients with advanced stage disease, the gynecologic oncologist must rely upon naked eye visual inspection and, if applicable, palpation. As a result, malignant tissue may remain undetected. Tumour-targeted molecular imaging using agents that specifically bind to cell-surface proteins overexpressed on EOC can improve intraoperative tumour detection. Our previous research using a fluorescent folate analogue during cytoreductive surgery has shown a detection of 29% additional metastatic EOC lesions. Yet, some false positive lymph nodes were found. This study aimed to determine which cell-surface proteins are suitable as an additional target for tumour-targeted molecular imaging of EOC metastases.
Methodology Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissues from primary ovarian tumours, lymph node, omental and peritoneal metastases from 84 EOC patients who underwent cytoreductive surgery. Tumour-negative tissue specimens were included as a control. The following cell-surface proteins were tested: EGFR (epithelial growth factor receptor), VEGF-A (vascular endothelial growth factor-A), L1CAM (L1 cell adhesion molecule), integrin avb6 and EpCAM (epithelial cell adhesion molecule). FRa (folate receptor alpha) was included as a reference.
Results EGFR, VEGF-A and L1CAM expression was observed in tumour-negative tissues. In EOC metastases, avb6 showed heterogenous expression patterns. As compared to FRa, EpCAM showed an equally high expression in these metastases. Furthermore, although EpCAM was expressed on tumour-negative epithelial cells lining the intestinal lumen, it was not expressed in lymph nodes that were previously false positive using the fluorescent folate analogue.
Conclusion In addition to FRa, EpCAM is a suitable target for tumour-targeted molecular imaging of EOC metastases and can contribute to a more reliable detection of EOC lesions intraoperatively. Further research will focus on examining whether serosal metastases can be accurately distinguished from the small bowel.
Disclosure This work was financially supported by the Zabawas Foundation, which was not involved in any part of the study. The authors have no conflicts of interest to disclose.
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