Biomarkers expression among paired serous ovarian cancer primary lesions and their peritoneal cavity metastases in treatment‐naïve patients: A single‐center study

Abstract

Background High‐grade serous ovarian carcinoma (HGSOC), the most common histologic subtype of ovarian epithelial cancer, is associated with treatment resistance, enhanced recurrence rates, and poor prognosis. HGSOCs often metastasize to the peritoneal cavity, while fluid cytology examination could identify such metastases. This retrospective study aimed to identify potential biomarker discrepancies between paired HGSOC primary tissues and metastatic peritoneal fluid cytology samples, processed as cell blocks (CBs). Methods Twenty‐four pairs of formalin‐fixed, paraffin‐embedded primary tissues and metastatic CBs from an equal number of treatment‐naïve patients were used, and immunohistochemistry (IHC) for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor, programmed cell death‐1 ligand 1 (PD‐L1), and CD147 was applied. Results 13/24 pairs showed discordant EGFR IHC results; in all these 13 patients, EGFR was positive (≥1+ membranous staining intensity found in at least 10% of the cancer cells) in the peritoneal, yet negative in the primary tissue samples. Notably, EGFR IHC was positive in 15/24 of the metastatic, whereas in just 2/24 of the primary HGSOC samples (p < 0.001). Although most PD‐L1 results were concordant, 5/24 and 6/24 pairs exhibited discordant results when stained with the E1L3N and 22C3 clones, respectively. Lastly, CD147 overexpression was found more often in the metastatic rather than the matched primary HGSOCs stained with CD147, though the difference was not significant. Conclusions Cytology from effusions could be considered for biomarker testing when present, even when tissue from the primary cancer is also available and adequately cellular, as it could provide additional information of potential clinical significance.

PD‐L1 immunohistochemical testing: A review with reference to cytology specimens

“…Liu et al 10 successfully performed immunocytochemical evaluation for PD‐L1 on specimens obtained from squamous cell carcinomas of the head and neck. Other studies have shown similar success for the use of cytologic material in the evaluation of PD‐L1 expression for melanomas, 9 ovarian peritoneal specimen, 11 and pancreatic adenocarcinomas 12 …”

“…The majority of the specimens in our review were non‐small cell lung adenocarcinomas, the review studies contained 23 melanomas, 9 21 squamous cell carcinomas of the head and neck, 10 24 cases of ovarian adenocarcinoma, 11 39 pancreatic carcinomas, 12 and 79 squamous cell carcinomas of the lung 13 …”

“…Current cytologic preparation techniques include direct smears, liquid‐based preparations including cytospins and cell block preparations. The majority of publications discussing PD‐L1 immunocytochemical staining have utilized cell block preparations 11,24,25,35,40,50,52,53,56 . A smaller number of manuscripts have discussed the use of direct smears, cell transfer techniques, cytospins, and liquid‐based preparations 9,18,52,53,59,60 .…”

“…Some authorities believe that alcohol fixation results in impaired immunohistochemical staining 63–66 and should be avoided with primary formalin fixation of cells blocks being the preferred technique. Other authors believe that the primary fixative has little impact of the quality of immunohistochemical staining and alcohol is not deleterious to the validity of PD‐L1 results 9–11,22,55,58–68 . Currently, the optimal technique for preparation of cell blocks remains in question but the majority of studies favor the use of primary formalin fixed paraffin embedded cell block material.…”

A Subset of Secreted Proteins in Ascites Can Predict Platinum-Free Interval in Ovarian Cancer

“…EMMPRIN from mesothelial cells has been shown to induce gastric cancer cell invasion [ 42 ]. Consistent with this possible mechanism, EMMPRIN was slightly elevated when metastatic HGSOC tumors were compared with matched primary tumors [ 43 ]. Analysis of ascites would detect either tumor cell or mesothelial cell-derived factors.…”