Soluble CD157 in pleural effusions: a complementary tool for the diagnosis of malignant mesothelioma

Our plain-English summary of Soluble CD157 in pleural effusions: a complementary tool for the diagnosis of malignant mesothelioma, by S. Augeri, S. Capano, S. Morone, et al (Oncotarget, 2018).

The study

• Authors: S. Augeri, S. Capano, S. Morone, G. Fissolo, A. Giacomino, S. Peola, Z. Drace, I. Rapa, S. Novello, M. Volante, L. Righi, E. Ferrero, E. Ortolan, A. Funaro
• Journal: Oncotarget
• Published: 2018;9(32):22785-22801
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: CD157/Bst1 glycoprotein is expressed in >85% of malignant pleural mesotheliomas and is a marker of enhanced tumor aggressiveness.

Results: In vitro, mesothelial cells (malignant and non-malignant) released CD157 in soluble form or as an exosomal protein. In vivo, sCD157 is released and can be measured in pleural effusions by ELISA. Significantly higher levels of effusion sCD157 were detected in patients with malignant pleural mesothelioma than in patients with non-mesothelioma tumors or with non-malignant conditions. In our patient cohort, the area under the receiver-operating characteristic curve for sCD157 that discriminated malignant pleural mesothelioma from all other causes of pleural effusion was 0.685, cut-off (determined by the Youden Index) = 23.66 ng/ml (62.3% sensitivity; 73.93% specificity). Using a cut-off that yielded 95.58% specificity, measurement of sCD157 in cytology-negative effusions increased sensitivity of malignant pleural mesothelioma diagnosis from 34.42% to 49.18%.

Conclusions: Evaluation of soluble CD157 in pleural effusions provides a diagnostic aid in malignant mesothelioma.

Methods: Soluble CD157 (sCD157) was detected biochemically in culture supernatants of malignant and non-malignant mesothelial cells, and in pleural effusions from various pathological conditions. An ELISA system was established to measure the concentration of sCD157 in fluids, and extended to analyze sCD157 in pleural effusions from a cohort of 295 patients.

In plain English

This laboratory and patient study from Torino, Italy, asked whether a protein called soluble CD157 (sCD157), measured in fluid around the lungs (pleural effusions), could help diagnose malignant pleural mesothelioma (MPM). The authors first showed that mesothelioma cells and non-malignant mesothelial cells grown in the laboratory released the protein. They then retrospectively measured it in effusions from 295 consecutive patients seen between November 2012 and October 2016: 61 with MPM, 129 with other cancers and 105 with non-malignant conditions. Levels were significantly higher in the MPM effusions than in the others. At a cut-off of 23.66 ng/ml, the test picked up 62.3% of MPM cases, with a specificity of 73.93% against all other effusions. Adding a higher cut-off to cytology raised effusion-based MPM diagnosis from 34.42% to 49.18% of MPM patients. Some high readings came from patients without cancer. sCD157 levels did not significantly predict survival. The authors concluded that sCD157 alone was not accurate enough for diagnosis but could support diagnosis when cytology is inconclusive. The study had no information on patients' asbestos exposure.

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: Laboratory study of cell lines, plus retrospective measurement of a candidate diagnostic marker (soluble CD157) in stored pleural effusion samples from consecutive patients
• Who was studied: 295 consecutive patients who underwent thoracentesis at San Luigi Gonzaga Hospital, Torino, Italy, between November 2012 and October 2016. 61 had malignant pleural mesothelioma (40 male, 21 female), 129 had other cancers (82 lung cancer, 47 non-lung cancer), and 105 had non-malignant conditions. Laboratory work also used one non-malignant mesothelial cell line and six mesothelioma cell lines.
• Exposure: Asbestos exposure was not studied; the authors had no information on it. The factor measured was the concentration of soluble CD157 in pleural effusions.
• Main results:
  • sCD157 concentration was significantly higher in effusions from the 61 MPM patients than in the 234 non-MPM effusions (P < 0.0001). Median levels were 31.02 ng/ml for MPM, 18.71 ng/ml for lung cancer, 19.8 ng/ml for other cancers and 18.6 ng/ml for non-malignant diseases.
  • For telling MPM apart from all other causes of effusion, the area under the ROC curve was 0.685 (95% CI 0.599 to 0.771).
  • At a cut-off of 23.66 ng/ml, sensitivity for MPM was 62.3% and specificity was 73.93%.
  • Using a high cut-off of 51.51 ng/ml (the 75th percentile), 9 of 162 cytology-negative effusions had high sCD157. Of these 9, 3 were from MPM patients, 2 from patients with a previous cancer, and 4 from patients with non-malignant diseases. Of 38 effusions classed as suspicious of malignancy, 6 had high sCD157, and all 6 were from MPM patients.
  • Combining cytology with sCD157 identified mesothelioma in 30 of 61 MPM patients, raising effusion-based diagnostic sensitivity from 34.42% (cytology alone) to 49.18%.
  • In 29 MPM biopsies, 12 of 18 with high CD157 staining had high effusion sCD157, compared with 3 of 11 with lower staining. The authors described this as a trend (P = 0.06).
  • Among 54 MPM patients with 1-year follow-up, 26 of 27 with high sCD157 died, compared with 17 of 27 with low sCD157 (P = 0.005).
  • Median survival was 10 months in MPM patients with high sCD157 and 16 months in those with low sCD157. The difference in overall survival was not statistically significant (P = 0.574).
• The authors' conclusion: The authors concluded that sCD157 alone is not accurate enough for diagnosis, but measuring it in effusions can provide supporting evidence for diagnosing MPM in people with symptoms when cytology is inconclusive.
• Limitations the authors state:
  • There were few patients with sarcomatoid and biphasic mesothelioma, so the comparison across tumor types needs further analysis.
  • The survival result needs careful interpretation because few patients were examined and the biphasic type was under-represented.
  • Independent validation in separate geographic cohorts, representing all mesothelioma types, is needed.
  • Four MPM effusions had virtually no sCD157, so a negative result does not rule out MPM. Biopsies from these patients could not be tested.
  • No information on asbestos exposure or on MPM stage was available, and exudates were not distinguished from transudates.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Mesothelioma, Glycoprotein, Pleural Mesothelioma, Mesothelial Cells, Cytology.

Related studies

• CD157 enhances malignant pleural mesothelioma aggressiveness and predicts poor clinical outcome — E. Ortolan, A. Giacomino, et al. (2014)
• Young investigator challenge: MicroRNA-21/MicroRNA-126 profiling as a novel tool for the diagnosis of malignant mesothelioma in pleural effusion cytology — R. Cappellesso, L. Nicolè, et al. (2016)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)
• Chest Imaging in the Diagnosis and Management of Pulmonary Tuberculosis: The Complementary Role of Thoraci Ultrasound — G. Rea, M. Sperandeo, et al. (2021)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary statement from the international mesothelioma interest group, also endorsed by the international academy of cytology and the papanicolaou society of cytopathology. A proposal to be applauded and promoted but which requires updating — M. Sheaff (2020)

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