Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study

Our plain-English summary of Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study, by F. Bruno, D. Baratti, A. Martinetti, et al (European Journal of Surgical Oncology, 2018).

The study

• Authors: F. Bruno, D. Baratti, A. Martinetti, D. Morelli, E. Sottotetti, C. Bonini, M. Guaglio, S. Kusamura, M. Deraco
• Journal: European Journal of Surgical Oncology
• Published: 2018;44(6):792-798
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients.

Methods: Markers were dosed before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) by enzyme-linked immunosorbent assay (ELISA) in 30 DMPM patients and 14 controls with other PSMs. Receiver-operating characteristics (ROC) curve were plotted. The performance of each marker was assessed by the area under the ROC curve (AUC-ROC).

Results: Mean mesothelin levels were 7.84 ng/dl (SD = 5.14) in DMPM group and 3.00 ng/dl (SD = 1.25) in controls (P = 0.001). Mean CEA levels were 5.3 ng/dl (SD = 4.7), and 61.96 ng/dl (SD = 112.5) in the two groups (P = 0.008). No statistical difference was seen for osteopontin (P = 0.738), CA19.9 (P = 0.081), CA125 (P = 0.600), and CA15.3 (P = 0.365). AUC-ROC was 0.836 for CA19.9, 0.812 for mesothelin, 0.793 for CEA, and lower for CA125 (0.652), osteopontin (0.531), and CA15.3 (0.481). Using diagnostic cut-offs selected by ROC methodology, sensitivity, specificity, positive and negative predictive values were 70.0%, 100.0%, 100.0%, and 60.9% for mesothelin >5.21 ng/dl, and 90.0%, 85.7%, 93.1%, and 80.0% for CA19.9 < 8.8 U/dl. At multivariate analysis, osteopontin correlated with survival (hazard rate 6.46; 95%CI 1.81-23.05; P = 0.004).

Conclusion: When assessing PSMs of unknown origin, elevated mesothelin with low CA19.9 may increase the suspicion index for DMPM. Ospeopontin warrants further investigations as a prognostic marker for DMPM.

Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

In plain English

This preliminary study from Milan, Italy, measured six blood markers, including mesothelin and osteopontin. It tested them in 30 patients with diffuse malignant peritoneal mesothelioma (DMPM) and 14 controls with other peritoneal surface malignancies, including multicystic mesothelioma, pseudomyxoma peritonei and cancers spread from the colon or appendix. All were selected for surgery with heated intraperitoneal chemotherapy (HIPEC) between 2009 and 2015; blood was taken shortly before surgery. Mean mesothelin was 7.84 ng/ml in DMPM patients and 3.00 ng/ml in controls, a statistically significant difference. Above 5.21 ng/ml, mesothelin identified 70.0% of DMPM patients and no controls. Osteopontin did not differ significantly between the groups. Among DMPM patients, the 5 with osteopontin above 11.408 ng/ml had a median survival of 9.3 months, compared with 36.0 months for the other 25. After adjustment for other factors, the hazard rate was 6.46 (95% CI 1.81 to 23.05). Asbestos exposure was not reported. The authors concluded that mesothelin, combined with markers of epithelial tumors, could help early assessment and that osteopontin might be a prognostic marker. They called for further study and noted the small, highly selected series.

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: Preliminary diagnostic and prognostic study of serum markers in prospectively selected and followed surgical patients, with a control group of patients with other peritoneal surface malignancies
• Who was studied: 30 patients with DMPM (25 epithelial, 5 biphasic) and 14 controls with other peritoneal surface malignancies, all selected for cytoreductive surgery and HIPEC at the National Cancer Institute, Milan, Italy, March 2009 to October 2015. The controls had serous-papillary peritoneal carcinoma (1), desmoplastic small round cell tumor (1), pseudomyxoma peritonei from low-grade appendiceal mucinous neoplasms (4), multicystic mesothelioma (2), and peritoneal metastases from colorectal cancer (2), appendiceal mucinous carcinoma (3) and appendiceal MANEC (1).
• Exposure: Not an asbestos exposure study. What was measured was preoperative serum levels of mesothelin, osteopontin, CEA, CA19.9, CA125 and CA15.3. Asbestos exposure of patients was not reported.
• Main results:
  • Mean serum mesothelin was 7.84 ng/ml (SD 5.14) in the DMPM group and 3.00 ng/ml (SD 1.25) in controls, P = 0.001 (Table 2)
  • Using a cut-off of 5.21 ng/ml, mesothelin had 70.0% sensitivity, 100% specificity and 100% positive predictive value for DMPM versus other peritoneal surface malignancies
  • Differences between DMPM patients and controls were not statistically significant for osteopontin, CA125 and CA15.3. CA19.9 was significantly higher in controls (P = 0.008).
  • CA19.9 at or below 37 U/ml was associated with 100.0% sensitivity and 100.0% negative predictive value for DMPM, but 35.7% specificity and 76.9% positive predictive value
  • Area under the ROC curve was 0.836 for CA19.9 and 0.812 (95% CI 0.666 to 0.913) for mesothelin, with lower values for CA125 (0.652), osteopontin (0.531) and CA15.3 (0.481)
  • In male patients only, mesothelin AUC (0.853) was statistically higher than CA125 AUC (0.494; 95% CI 0.298 to 0.692; P = 0.001) and CA15.3 AUC (0.482)
  • In DMPM patients, median survival was 36.0 months for the 25 with osteopontin at or below 11.408 ng/ml and 9.3 months for the 5 above it (P = 0.001)
  • After adjustment for completeness of cytoreduction, histology and lymph-node status, higher osteopontin remained associated with survival (hazard rate 6.46; 95% CI 1.81 to 23.05; P = 0.004)
  • Median survival was 20.8 months for DMPM patients with mesothelin above 5.21 ng/ml versus 48.8 months for those below it, a difference that was not statistically significant (P = 0.494)
• The authors' conclusion: The authors concluded that serum mesothelin combined with markers of epithelial tumors may help in the early assessment of peritoneal disease of unknown origin, that osteopontin might be a prognostic marker for selecting DMPM patients for aggressive treatment, and that both markers need further clinical study
• Limitations the authors state:
  • Small number of patients
  • Highly selected series that may not represent the general DMPM population
  • The study was not powered for the prognostic analysis, which was a secondary objective
  • Survival was lower than in earlier DMPM series, which may have hampered the analysis of prognostic factors
  • No information on mesothelin as a marker of tumor response or in postoperative surveillance

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelin, Osteopontin, Peritoneal Mesothelioma, Differential Diagnosis, Pleural Mesothelioma, Cytoreductive Surgery, HIPEC, Multivariate Analysis.

Related studies

• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)
• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)
• Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma — I. Pantazopoulos, P. Boura, et al. (2013)

Browse more research in European Journal of Surgical Oncology, or return to medical research.