Article Text
Abstract
Introduction/Background In advanced stage high grade serous ovarian cancer (HGSOC), the peritoneum is the primary site of disease recurrence in >75% of patients despite complete cytoreductive surgery and chemotherapy. Macroscopically undetectable remaining cancer cells are deemed to be a source for recurrent disease. We investigated characteristics of occult disease in biopsies of macroscopically normal peritoneum during surgery.
Methodology We included 14 patients, of which eleven patients had received neoadjuvant chemotherapy and three patients were chemotherapy naïve. Each patient underwent study-related peritoneal biopsies of healthy looking peritoneum adjacent to a metastasis and at distance from metastases. Sections were immunohistochemically stained for PAX8 and PanCK as markers of HGSOC cells. Additionally in 4 patients we have biopsied the macroscopically healthy peritoneum three times. We selected 8 high quality biopsies for combined immunofluorescence staining for PAX8 and SOX2 as a marker for cancer stem cell properties.
Results Macroscopically normal peritoneum showed solitary PAX8-positive cells adjacent to and at distance from metastases in all patients. Thirteen percent of these PAX8-positive cells were found to be attached to the mesothelium and are presumably spread through intra-abdominal fluid. Eighty-seven percent of cells were found in the stroma underneath the mesothelium, of which 59% were firmly attached to endothelium and 33% were found in the stroma. Additional immunofluorescence staining showed simultaneous SOX2 and PAX8 positivity in all 8 biopsies. Chemotherapy did not affect these results.
Conclusion Solitary PAX8-positive cells are present in the macroscopically healthy-looking peritoneum of all EOC patients investigated, irrespective of the distance to macroscopically-visible metastases and of previous treatment. The majority of these solitary cancer cells were attached to endothelium of vascular or lymphatic vessels. Their solitary character and lack of proliferation combined with SOX2-positivity suggests a stem cell state, which could explain why these cells are unaffected by neo-adjuvant chemotherapy.
Disclosures We are currently in the proces of collecting a larger sample set to further investigate this phenomenon.