The importance of serum and pleural fluid level of vascular endothelial growth factor (VEGF) and VEGF fluid/serum ratio in the differential diagnosis of malignant mesothelioma-related pleural effusion

Our plain-English summary of The importance of serum and pleural fluid level of vascular endothelial growth factor (VEGF) and VEGF fluid/serum ratio in the differential diagnosis of malignant mesothelioma-related pleural effusion, by Y. Düzköprü, Z. Oruç, M.A. Kaplan, et al (Contemporary Oncology = Współczesna Onkologia, 2017).

The study

• Authors: Y. Düzköprü, Z. Oruç, M.A. Kaplan, R. Ülkü, Ç. Tanrıkulu, D. Esmer, A. Bırak, M. Küçüköner, Z. Urakçı, A. Işıkdoğan
• Journal: Contemporary Oncology = Współczesna Onkologia
• Published: 2017;21(3):213-217
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Aim Of The Study: Vascular endothelial growth factor (VEGF) is one of the parameters that has been studied in differential diagnosis of malignant fluids. This study is aimed at evaluate applicability of serum, fluid VEGF level and fluid to serum VEGF ratio in the diagnosis of malignant pleural mesothelioma (MPM).

Material And Methods: The patients with pleural effusion over age of 18, between 2011 and 2015 were included in the study. They were divided into three groups: group 1 - mesothelioma patients; group 2 - other malignancies; and group 3 - benign aetiologies. Group 1 and 2 were termed as the malignant group. Fluid, serum VEGF levels, and the ratio of fluid/serum VEGF level were studied to evaluate the fluid/serum VEGF ratio in all groups.

Results: Twenty cases with mesothelioma, 44 cases with other malignancies, and 20 cases with benign aetiologies were included in this study. No statistically significant difference was found according to serum VEGF levels for all groups, (group 1: 437 ±324 pg/ml, group 2: 354 ±223 pg/ml, group 3: 373 ±217 pg/ml, p = 0.836), while fluid VEGF levels showed a statistically significant difference (group 1: 3359 ±700 pg/ml, group 2: 2175 ±435 pg/ml, group 3: 1092 ±435 pg/ml, p = 0.041). The ratio of fluid to serum VEGF levels showed a difference, at the significance limit, between the malignant (group 1 and group 2) and benign (group 3) groups (8.83 ±1.29 vs. 4.57 ±1.07, p = 0.059) but showed a statistically significant difference between the mesothelioma and benign groups (12.11 ±1.68 vs. 4.57 ±1.07, p = 0.044).

Conclusions: The VEGF fluid/serum ratio may be an applicable parameter in the differential diagnosis of malignant fluids, especially MPM.

In plain English

This prospective study measured a protein called vascular endothelial growth factor (VEGF) in the lung-lining fluid and blood serum of 84 adults with fluid around the lungs (pleural effusion). They were diagnosed at Dicle University hospital in Turkey, 2011 to 2015. Twenty had malignant pleural mesothelioma, 44 had other cancers and 20 had non-cancer causes. Average fluid VEGF differed among groups (3359 pg/ml in mesothelioma, 2175 in other cancers, 1092 in benign cases; p = 0.041). Only the mesothelioma-versus-benign difference was statistically significant (p = 0.014). Serum VEGF did not differ significantly. The fluid-to-serum ratio was 12.11, 7.19 and 4.57 respectively. The mesothelioma-versus-benign difference was significant (p = 0.044). All cancers versus benign narrowly missed significance (p = 0.059). At a cut-off ratio of 0.85, used to separate all cancer patients from benign cases, the ratio showed 76% sensitivity and 50% specificity. The authors concluded VEGF can be useful, particularly for mesothelioma, but needs further study and should be used with other tests. They noted the small numbers and a mixed benign group. The article does not discuss 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: Prospective diagnostic marker study comparing three patient groups
• Who was studied: 84 patients over age 18 diagnosed with pleural effusion at Dicle University Faculty of Medicine hospital, Turkey, 2011 to 2015. Group 1 had 20 patients with histologically confirmed mesothelioma (14 epithelial, 1 sarcomatoid, 2 biphasic, 3 unknown subtype). Group 2 had 44 patients with other cancers, 18 of them lung cancer. Group 3 had 20 patients with benign causes (heart failure, renal failure, pneumonia, liver cirrhosis). Patients on anti-inflammatory drugs, corticosteroids or anticancer therapy were excluded.
• Exposure: Not reported. The article does not describe asbestos or occupational exposure. What was measured was VEGF in pleural fluid and serum, using an ELISA test.
• Main results:
  • Mean pleural fluid VEGF was 3359 ±700 pg/ml in the mesothelioma group, 2175 ±435 pg/ml in the other-cancer group and 1092 ±435 pg/ml in the benign group (p = 0.041).
  • For fluid VEGF, only the mesothelioma-versus-benign difference was statistically significant (p = 0.014). Mesothelioma versus other cancers (p = 0.233) and other cancers versus benign (p = 0.086) were not.
  • Mean serum VEGF did not differ significantly: 437 ±324 pg/ml in mesothelioma, 354 ±223 pg/ml in other cancers and 373 ±217 pg/ml in benign cases (p = 0.836).
  • The fluid/serum VEGF ratio was 12.11 ±1.68 in mesothelioma, 7.19 ±1.04 in other cancers and 4.57 ±1.07 in benign cases (overall p = 0.10).
  • The fluid/serum ratio in all cancer patients combined (8.83 ±1.29) versus benign patients (4.57 ±1.07) was at the significance limit (p = 0.059).
  • The fluid/serum ratio difference between the mesothelioma and benign groups was statistically significant (p = 0.044).
  • A ROC analysis set a fluid/serum ratio cut-off of 0.85 between the malignant (all cancers combined) and benign groups. At that cut-off the ratio had 76% sensitivity and 50% specificity.
  • When patients were grouped by a cut-off ratio of 0.85, the difference between all cancers and the benign group was statistically significant (p = 0.032). The mesothelioma-versus-benign difference was at the significance limit (p = 0.076).
• The authors' conclusion: The authors concluded that VEGF can be a useful parameter in telling malignant pleural fluids apart, particularly malignant pleural mesothelioma. They said further studies are needed and these parameters should be evaluated together with others.
• Limitations the authors state:
  • Limited number of cases, and a benign group made up of different conditions.
  • Some results at the significance limit might be due to the small sample size.

Topics

Medical terms in this study, explained in our Lexicon: Differential Diagnosis, Mesothelioma, Pleural Effusion, Pleural Mesothelioma.

Related studies

• Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications — A. Fiorelli, G. Vicidomini, et al. (2011)
• Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma — A. Yasumitsu, C. Tabata, et al. (2010)
• Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma — N. Fujimoto, K. Gemba, et al. (2011)
• The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor — P. Cacciotti, L. Strizzi, et al. (2002)
• Utility of hyaluronic acid in pleural fluid for differential diagnosis of pleural effusions: likelihood ratios for malignant mesothelioma — S. Atagi, M. Ogawara, et al. (1997)
• Differences in Pleural Fluid Amylase Levels in Patients with Malignant Pleural Effusion Based on Cancer Type, Histologic Type, and Epidermal Growth Factor Receptor Mutations — M. Shimoda, Y. Tanaka, et al. (2023)

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