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

Our plain-English summary of Improving the cytological diagnosis of high-grade serous carcinoma in ascites with a panel of complementary biomarkers in cell blocks, by X. Zhang, L. Chen, Y. Liu, et al (Cytopathology, 2018).

The study

• Authors: X. Zhang, L. Chen, Y. Liu, Y. Xu, X. Zhang, Y. Shi, C. Wang, P.L. Zhang, Y. Liu
• Journal: Cytopathology
• Published: 2018;29(3):247-253
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

© 2017 The Authors. Cytopathology Published by John Wiley & Sons Ltd.

In plain English

This retrospective study from Tianjin Central Hospital of Gynecology Obstetrics in China looked at abdominal fluid (ascites) or peritoneal washings. The samples were collected after surgery from 2012 to 2015 from 253 patients with confirmed high-grade serous carcinoma, a pelvic cancer. The study did not examine asbestos exposure. The 70 samples whose cells looked atypical were tested with antibody stains meant to tell cancer cells from mesothelial cells, the cells that line the abdomen. Standard haematoxylin and eosin staining served as the reference. Used alone, Ber-EP4 detected cancer with 85.7% sensitivity and 82.1% specificity. HBME-1 identified mesothelial cells with 100% sensitivity and 68.3% specificity. In 29 samples stained with all four markers, Ber-EP4 plus E-cadherin reached 100% sensitivity and 88.9% specificity for cancer, and HBME-1 plus calretinin reached 100% and 90% for mesothelial cells. Among 16 patients whose fluid was sampled before surgery, 15 had tumour cells, but only six were diagnosed with this cancer before surgery. The authors concluded that this four-marker panel is valuable and ideal for diagnosing the cancer from ascites.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective diagnostic accuracy study of immunostaining markers on ascites cell blocks, with haematoxylin and eosin staining as the reference standard
• Who was studied: Ascites or peritoneal washings from 253 patients with histologically confirmed high-grade serous carcinoma (pelvic, ovarian, fallopian tube or peritoneal) at Tianjin Central Hospital of Gynecology Obstetrics, China, 2012 to 2015. 183 cases with typical tumour appearance were excluded, and 70 atypical cases were analysed. 29 cases were stained with all four main markers.
• Main results:
  • In 70 cases, Ber-EP4 (a cancer cell marker) had a sensitivity of 85.7% (36/42) for tumour cells
  • In 70 cases, Ber-EP4 had a specificity of 82.1% (23/28)
  • In 69 cases, HBME-1 (a mesothelial cell marker) had a sensitivity of 100% (28/28) for mesothelial cells
  • HBME-1 specificity was 28/41, printed as 68.2% in the results text and 68.3% in the abstract and Table 2
  • In 29 cases, E-cadherin had a sensitivity of 95% (19/20) for tumour cells
  • In 29 cases, E-cadherin had a specificity of 33.3% (3/9)
  • In 29 cases, calretinin had a sensitivity of 88.9% (8/9) for mesothelial cells
  • In 29 cases, calretinin had a specificity of 90% (18/20)
  • In the 29 cases stained with all four markers, Ber-EP4 combined with E-cadherin gave 100% sensitivity and 88.9% specificity for detecting high-grade serous carcinoma
  • In the same 29 cases, HBME-1 combined with calretinin gave 100% sensitivity and 90% specificity for identifying mesothelial cells
  • Among 16 patients with ascites sampled before surgery, 15 were confirmed positive for tumour cells
  • In the preoperative samples, P53 was positive in 54.5% (6/11) and PAX-8 in 58.3% (7/12)
  • Only six of the preoperative cases were diagnosed as high-grade serous carcinoma before surgery
  • The authors stated that P53 and PAX-8 are not very sensitive for this diagnosis from ascites, so negative staining for them does not fully exclude it
• The authors' conclusion: The authors concluded that the panel of complementary markers (Ber-EP4, E-cadherin, HBME-1 and calretinin) is valuable and ideal for the differential diagnosis of high-grade serous carcinoma from ascites cytology.

Topics

Medical terms in this study, explained in our Lexicon: Carcinoma, Ascites, Biomarker, Cell Block, Staging, Reactive Mesothelial Hyperplasia, Ber-EP4, HBME-1.

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