The use of pleural fluid sCD44v6/std ratio for distinguishing mesothelioma from other pleural malignancies

Our plain-English summary of The use of pleural fluid sCD44v6/std ratio for distinguishing mesothelioma from other pleural malignancies, by J.M. Porcel, A. Esquerda, F. Rodriguez-Panadero, et al (Journal of Thoracic Oncology, 2011).

The study

• Authors: J.M. Porcel, A. Esquerda, F. Rodriguez-Panadero, A. Martínez-Iribarren, S. Bielsa
• Journal: Journal of Thoracic Oncology
• Published: 2011;6(1):190-4
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Differentiating metastatic adenocarcinoma from malignant pleural mesothelioma is often a challenging task. Spliced forms of CD44, such as exon v6 (CD44v6), have been implicated in tumor metastasis. We examined the diagnostic performance of soluble (s) CD44v6 and CD44 standard (sCD44std) as biomarkers for nonmesothelioma pleural malignancies in a retrospective series.

Methods: The pleural fluid from 161 patients with pleural effusion (33 mesotheliomas, 104 nonmesothelioma malignancies, and 24 benign conditions) was analyzed for sCD44v6 and sCD44std levels using an enzyme-linked immunosorbent assay kit. The ability of sCD44v6 and sCD44std levels and the sCD44v6/std ratio for distinguishing mesothelioma from nonmesothelioma malignancy were examined.

Results: Median pleural fluid concentrations of sCD44v6 but not sCD44std were significantly higher in patients with nonmesothelioma malignancy (101.5 ng/mL) than in those with mesothelioma (38 ng/mL, p < 0.0001). Fluids from metastatic squamous cell carcinomas exhibited particularly high sCD44v6 levels (388 ng/mL). A cutoff value of 100 ng/mL had the highest accuracy for distinguishing mesothelioma from nonmesothelioma malignancy (sensitivity 53% and specificity 88%) or metastatic adenocarcinoma (sensitivity 60% and specificity 88%). An sCD44v6/std ratio of more than 0.34 discriminated between adenocarcinoma and mesothelioma with a sensitivity of 60%, a specificity of 93%, a likelihood ratio positive of 9.97, and an area under the curve of 0.87 (95% confidence interval: 0.80-0.94).

Conclusions: The pleural fluid sCD44v6/std ratio may be a new diagnostic marker in the differential diagnosis between primary mesothelioma and other pleural malignancies. Values greater than 0.34 predict nonmesothelioma malignancy and may be a help in determining whether an invasive thoracoscopy is necessary.

In plain English

This retrospective study from two Spanish university hospitals tested whether two proteins in the fluid around the lungs, soluble CD44 standard (sCD44std) and soluble CD44v6 (sCD44v6), could distinguish malignant pleural mesothelioma from other pleural cancers. The authors analyzed stored pleural fluid, collected 1995 to 2009, from 161 patients: 33 with mesothelioma, 48 with metastatic adenocarcinoma, 39 with lymphoma, 17 with metastatic squamous cell carcinoma, and 24 with benign effusions. sCD44std levels did not differ significantly between groups. Median sCD44v6 was lower in mesothelioma (38 ng/mL) than in the other cancers combined (101.5 ng/mL). A ratio of sCD44v6 to sCD44std above 0.34 separated metastatic adenocarcinoma from mesothelioma with 60% sensitivity (95% confidence interval 46 to 74%), 93% specificity (85 to 100%), and an area under the curve of 0.87 (0.80 to 0.94). The authors noted a ratio below 0.34 did not lower the probability of adenocarcinoma enough to be clinically meaningful. The markers were not significantly linked with survival. The authors concluded the ratio could be a helpful diagnostic adjunct and called for prospective validation. The study did not examine 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: Retrospective diagnostic accuracy study using stored pleural fluid samples from two hospital biobanks; laboratory staff were blinded to diagnoses
• Who was studied: 161 patients (93 men, 68 women; median age 65) with pleural effusion at two Spanish university hospitals (Arnau de Vilanova, Lleida, and Virgen del Rocio, Sevilla), samples collected 1995 to 2009. The groups were 33 mesotheliomas (29 epithelioid, 2 sarcomatoid, 2 biphasic), 48 metastatic adenocarcinomas, 39 lymphomas, 17 metastatic squamous cell carcinomas and 24 benign effusions. The 104 nonmesothelioma malignancies included the lymphomas.
• Exposure: Not studied. Asbestos exposure was not measured; it is mentioned only in the discussion as a clinical factor that may influence decisions. The study measured pleural fluid levels of sCD44std and sCD44v6 by ELISA.
• Main results:
  • Pleural fluid sCD44std levels did not differ significantly among the patient groups.
  • Median sCD44v6 was significantly lower in patients with mesothelioma (38 ng/mL) than in those with nonmesothelioma malignancies (101.5 ng/mL). It was also significantly lower than in patients with benign conditions (64.5 ng/mL).
  • The median sCD44v6 to sCD44std ratio was significantly lower in the mesothelioma group (0.18) than in patients with nonhematologic metastatic tumors (0.5).
  • Metastatic squamous cell carcinomas had higher sCD44v6 (388 ng/mL) and higher ratios (0.64) than any other cause of pleural effusion (83 ng/mL and 0.25).
  • In the tables, an sCD44v6 cutoff of 100 ng/mL identified nonmesothelioma malignancy against mesothelioma with sensitivity 52% (95% CI 43 to 62) and specificity 87% (95% CI 76 to 99). For adenocarcinoma versus mesothelioma, the same cutoff gave sensitivity 60% (95% CI 46 to 74) and specificity 87% (95% CI 76 to 99).
  • A sCD44v6/std ratio greater than 0.34 separated metastatic adenocarcinoma from pleural mesothelioma with sensitivity 60% (95% CI 46 to 74), specificity 93% (95% CI 85 to 100) and positive likelihood ratio 9.97 (95% CI 2.55 to 38.95).
  • The area under the ROC curve for the ratio in differentiating adenocarcinoma from mesothelioma was 0.87 (95% CI 0.80 to 0.94).
  • The authors stated that a ratio below 0.34 did not reduce the probability of adenocarcinoma enough to be clinically meaningful (likelihood ratio about 0.4).
  • Mesothelioma patients with sCD44v6 above 100 ng/mL or a ratio above 0.34 showed a trend toward shorter median survival (10 versus 17 months), but this was not statistically significant (p values of 0.391 and 0.982).
• The authors' conclusion: The authors concluded that the sCD44v6/std ratio could be a helpful adjunct in the differential diagnosis of malignant pleural effusions. In their view, it could identify effusions with a high probability of being metastatic and so avoid invasive thoracoscopy in the right clinical setting.
• Limitations the authors state:
  • The findings come from a retrospective analysis and need prospective evaluation in an independent validation cohort.
  • It is not yet known how the tests perform in patients whose cytology results are uncertain or falsely negative, as opposed to well-defined populations.
  • Histology remains the gold standard for diagnosis.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Adenocarcinoma, Pleural Mesothelioma, Metastasis, Biomarker, Pleural Effusion, Squamous Cell Carcinoma, confidence interval.

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