Improving the cytological diagnosis of high‐grade serous carcinoma in ascites with a panel of complementary biomarkers in cell blocks

Abstract

Introduction Precise cytological diagnosis of pelvic high‐grade serous carcinoma (HGSC) in ascites is important for tumour staging, therapeutic decision‐making and prognostic evaluation. However, it can often be difficult to distinguish metastatic HGSC cells from reactive mesothelial cells based on morphology alone. Immunocytochemical analysis of ascites cell blocks has been used to obtain accurate diagnosis and provide a reliable basis for treatment decisions in the clinic. This study was performed to determine whether a panel of antibodies is necessary to achieve high specificity and sensitivity for the identification of HGSC cells. Methods Ascites samples from 70 cases (70/253, 27.7%) of histologically confirmed HGSC were postoperatively collected from 2012 to 2015 and were immunocytochemically analysed. Results The sensitivity and specificity of Ber‐EP4 (a marker of HGSC) for detecting HGSC was 85.7% and 82.1%, respectively, whereas the sensitivity and specificity of HBME‐1 for identifying mesothelial cells was 100% and 68.3%, respectively. To improve the rate of detection further of HGSC, 29 cases of ascites were also stained for E‐cadherin (a marker of HGSC) and calretinin (a marker of mesothelial cells). The combination of Ber‐EP4 and E‐cadherin as markers of adenocarcinoma cells increased the sensitivity and specificity for HGSC detection to 100% and 88.9%, respectively. Meanwhile, the sensitivity and specificity for mesothelial cell identification increased to 100% and 90%, respectively, when HBME‐1 and calretinin were combined. Conclusion This panel of complementary biomarkers is valuable and ideal for the differential diagnosis of HGSC based on ascites cytology.

Disposable Amperometric Immunosensor for the Determination of the E‐Cadherin Tumor Suppressor Protein in Cancer Cells and Human Tissues

“…These authors also stated that current tests for E‐cad lack sensitivity and specificity. Methodologies mainly used for E‐cad protein detection include immunohistochemistry or immunocytochemistry for tissue samples or cell lines, and ELISA tests for biological fluids , these last ones with a declared sensitivity of 0.039 ng mL −1 .…”

Cytomorphology and immunocytochemical features of ovarian granulosa cell tumors in ascites or peritoneal washings: A retrospective review

“…Negative staining for MC, CK5/6, and BerEP4 may exclude both mesothelial and epithelial cells 19,20 and positive for WT1, vimentin and negative for CK7 may confirm the diagnosis of OGCT cells, as most OGCT show this kind of immunophenotype. Occasionally, AGCT with a diffuse pattern can be mistaken for a poorly differentiated carcinoma 12,21 . Cytomorphologic features can be very helpful in differential diagnosis as granulosa cells usually show relatively uniform nuclei, and some are often grooved, while poorly differentiated carcinomas with nuclear atypia and mitosis are commonly seen and, usually display hyperchromatic and pleomorphic nuclei without nuclear grooves.…”

Cytopathological assessment is an accurate method for identifying immunophenotypic features and BRCA1/2 mutations of high‐grade serous carcinoma from ascites

“…We have postulated that ICC assessments of PAX8, WT1, P53, P16, and Ki‐67 on ascites cytospins and cytoblocks can provide the same information as the primary tumor tissue for the accurate immunophenotyping of HGSC and detection of germline and somatic BRCA1/2 mutations. So far, the sensitivity and specificity of cytopathology for differentiating tumor cells and mesothelial cells in ascites have been proven, 7 yet only a few studies have focused on immunophenotypic features of HGSC. For instance, Bansal et al 12 .…”

“…5,6 Cytospin and cytoblock immunocytochemistry (ICC) has been proven to be highly sensitive and specific for distinguishing HGSC cells from reactive mesothelial cells and other malignant cells in ascites. 7 Yet, it is not clear whether cytoblock ICC can provide an accurate assessment of the immunophenotypic features of HGSC from ascites, and studies on cytospin ICC have not yet been reported. As for the BRCA1/2 status, our group has recently reported that cytopathological specimens (ascites, pleural effusions, and lymph node fine-needle aspirates) of HGSC can be alternatives to primary tumor biopsy for the detection of BRCA1/2 mutations.…”

“…Cytopathological examination of ascites is an appealing minimally invasive method for assessing immunophenotypic features of HGSC and BRCA1/2 mutations 5,6 . Cytospin and cytoblock immunocytochemistry (ICC) has been proven to be highly sensitive and specific for distinguishing HGSC cells from reactive mesothelial cells and other malignant cells in ascites 7 . Yet, it is not clear whether cytoblock ICC can provide an accurate assessment of the immunophenotypic features of HGSC from ascites, and studies on cytospin ICC have not yet been reported.…”