Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment

Our plain-English summary of Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment, by B.D. Grigoriu, A. Scherpereel, P. Devos, et al (Clinical Cancer Research, 2007).

The study

• Authors: B.D. Grigoriu, A. Scherpereel, P. Devos, B. Chahine, M. Letourneux, P. Lebailly, M. Grégoire, H. Porte, M.C. Copin, P. Lassalle
• Journal: Clinical Cancer Research
• Published: 2007;13(10):2928-35
• Cited by: 160 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Malignant mesothelioma is a highly aggressive tumor and is often diagnosed too late for a curative treatment. We compared diagnostic and prognostic values of mesothelin and osteopontin in 172 patients suspected of malignant pleural mesothelioma (MPM) and in a control group of 112 asymptomatic asbestos-exposed subjects.

Experimental Design: Osteopontin and mesothelin were assayed with commercial ELISA kits in a series of 43 patients with pleural metastases of various carcinomas, 33 patients with benign pleural lesions associated with asbestos exposure, 96 patients with MPMs, and 112 asbestos-exposed healthy subjects. Results were correlated with patient's diagnosis and survival.

Results: Serum osteopontin level was higher in MPM patients compared with healthy asbestos-exposed subjects and had a good capability to distinguish between these two populations. However, osteopontin was unable to distinguish between MPM and pleural metastatic carcinoma or benign pleural lesions associated with asbestos exposure. Neither plasma nor pleural fluid osteopontin were more powerful in this respect. Serum mesothelin had a good ability for diagnosing MPM but was unable to identify patients with nonepithelioid mesothelioma subtypes. Survival analysis identified tumor histologic subtype along with serum osteopontin and serum mesothelin as independent prognostic factors in mesothelioma patients.

Conclusions: Osteopontin has a lower diagnostic accuracy than mesothelin in patients suspected of MPM. Insufficient specificity limits osteopontin utility as diagnostic marker. Both molecules have a potential value as prognostic markers.

In plain English

Researchers at 20 departments in northern and western France tested whether osteopontin and mesothelin, proteins measured mainly in blood, help diagnose malignant pleural mesothelioma and predict survival. From May 2003 they recruited 172 consecutive patients suspected of, or recently diagnosed with, the disease. Of these, 96 had mesothelioma, 43 had other cancers spread to the pleura, and 33 had benign asbestos-related pleural lesions. Also tested were 112 healthy asbestos-exposed workers from a textile and friction material facility. Serum osteopontin was higher in mesothelioma patients than in healthy exposed workers (median 69.9 versus 34.7 ng/mL), but it did not differ significantly between the three patient groups. Serum mesothelin was higher in mesothelioma patients than in all other groups, though values were low in sarcomatoid and biphasic subtypes. In 91 mesothelioma patients with follow-up, three factors were independently linked with shorter survival: high serum mesothelin (above 3.5 nmol/L), high serum osteopontin (above 350 ng/mL) and sarcomatoid subtype. The authors concluded that insufficient specificity limits osteopontin's usefulness as a diagnostic marker, but that both proteins may have prognostic value.

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: Diagnostic and prognostic biomarker study: consecutive patients suspected of, or recently diagnosed with, malignant pleural mesothelioma, compared with a control cohort of healthy asbestos-exposed workers, with survival follow-up
• Who was studied: 172 patients suspected of, or recently diagnosed with, malignant pleural mesothelioma, recruited from May 2003 at 20 pulmonary or thoracic surgery departments in the north and west of France. Final diagnosis: 96 with mesothelioma (73 epithelioid, 10 sarcomatoid, 13 biphasic), 33 with benign pleural lesions associated with asbestos exposure, and 43 with pleural metastasis of various carcinomas. Controls were 112 asymptomatic asbestos-exposed workers recruited December 2001 to June 2004. Of the 172 patients, 119 were also included in the authors' earlier mesothelin report.
• Exposure: Occupational asbestos exposure; fiber types are not given. The control workers were exposed at a single facility processing textile and friction materials. Confirmed asbestos exposure was recorded in 82 of 96 mesothelioma patients (85.4%), 28 of 33 benign-lesion patients (84.8%), 15 of 43 metastasis patients (34.9%) and all 112 controls. The markers studied were osteopontin (serum, plasma, pleural fluid) and mesothelin (serum, pleural fluid), both measured with commercial ELISA kits.
• Main results:
  • Median serum osteopontin was 34.7 ng/mL in the healthy asbestos-exposed group. It was higher in patients with benign asbestos-related pleural lesions (median 50.4 ng/mL, P = 0.006), mesothelioma (median 69.9 ng/mL, P = 0.001) and pleural metastases (median 89.8 ng/mL, P = 0.001).
  • Serum osteopontin did not differ significantly between the three patient groups (mesothelioma, metastases, benign lesions; P > 0.38 for all comparisons).
  • Serum osteopontin distinguished mesothelioma patients from healthy asbestos-exposed subjects with an AUC of 0.724 (95% CI, 0.650-0.798).
  • Pleural fluid osteopontin was slightly higher in mesothelioma patients than in the metastasis and benign-lesion groups, but the differences were not statistically significant.
  • Serum mesothelin was significantly higher in mesothelioma patients (median 1.94 nmol/L) than in the metastasis, benign-lesion and healthy exposed groups (P < 0.001 for all comparisons). Median values were low in sarcomatoid or biphasic mesothelioma (data not shown).
  • Serum mesothelin distinguished mesothelioma patients from healthy exposed subjects (AUC 0.866; 95% CI, 0.811-0.920), from benign-lesion patients (AUC 0.834; 95% CI, 0.755-0.912) and from metastasis patients (AUC 0.719; 95% CI, 0.624-0.814).
  • Combining the two markers did not classify patients better than mesothelin alone.
  • Among 91 mesothelioma patients with follow-up, those with serum mesothelin above 3.5 nmol/L had a median survival of 7 months (95% CI, 3-11), compared with 19 months (95% CI, 13-25) for the low-mesothelin group (P = 0.003).
  • Mesothelioma patients with serum osteopontin above 350 ng/mL had a median survival of 5 months (95% CI, 2-8), compared with 15 months (95% CI, 11-19) for those with low levels.
  • In the multivariate analysis of mesothelioma patients, three factors remained significant but tumor stage did not: sarcomatoid subtype (HR 6.683; 95% CI, 2.525-17.683), serum mesothelin above 3.5 nmol/L (HR 2.785; 95% CI, 1.384-5.607) and serum osteopontin above 350 ng/mL (HR 3.459; 95% CI, 1.098-10.895). Sarcomatoid patients had a median survival of 5 months, compared with 17 months for both epithelioid and biphasic subtypes.
• The authors' conclusion: The authors concluded that osteopontin has lower diagnostic accuracy than mesothelin in patients suspected of malignant pleural mesothelioma. Osteopontin cannot tell mesothelioma apart from pleural metastatic carcinoma or benign asbestos-related pleural lesions, and its insufficient specificity limits its use as a diagnostic marker. The authors suggested it could at best serve as a first-step selection marker combined with a more specific assay. Serum mesothelin keeps diagnostic value but detects only the epithelioid subtype. Both serum markers have potential value as prognostic markers.
• Limitations the authors state:
  • Tumor stage was only marginally significant as a prognostic factor (P = 0.058), which the authors suggest may be due to an insufficient number of patients.
  • Complete staging was missing for 13 (13.5%) mesothelioma patients, which the authors attribute to the difficulty of staging without complete surgical investigation.
  • Osteopontin exists in several forms and fragments, and results depend on the assay used; the authors say the same applies to mesothelin.
  • Only serum was available for the healthy asbestos-exposed control subjects.

Topics

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

Medical terms in this study, explained in our Lexicon: Osteopontin, Mesothelin, Pleural Mesothelioma, Prognosis, Mesothelioma, Carcinoma, Asbestos Exposure, Histological Subtype.

Related studies

• 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)
• Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma — A. Scherpereel, B. Grigoriu, et al. (2006)
• Serum mesothelin has a higher diagnostic utility than hyaluronic acid in malignant mesothelioma — B. Grigoriu, B. Chahine, et al. (2009)
• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels — A.J. Rai, R.M. Flores, et al. (2010)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)

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