Mesothelin-related predictive and prognostic factors in malignant mesothelioma: a nested case-control study

Our plain-English summary of Mesothelin-related predictive and prognostic factors in malignant mesothelioma: a nested case-control study, by O.D. Roe, J. Creaney, S. Lundgren, et al (Lung Cancer, 2008).

The study

• Authors: O.D. Roe, J. Creaney, S. Lundgren, E. Larsson, H. Sandeck, P. Boffetta, T.I. Nilsen, B. Robinson, K. Kjaerheim
• Journal: Lung Cancer
• Published: 2008;61(2):235-43
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Soluble mesothelin-related protein (SMRP) in serum is potentially a sensitive marker of malignant mesothelioma (MM) diagnosis and progression, and may be useful as screening marker. Mesothelin expression in tumors is regarded as a sensitive marker for diagnosis and disease progression, and is a candidate prognostic marker. Levels of SMRP, CA125 and CYFRA 21-1 in pre-diagnostic (1-30 years) serum samples from 47 mesothelioma cases and 141 matched controls were analysed. Mesothelin expression in tumors was assessed. The association between biomarker level and mesothelioma risk and survival was analysed, adjusting for asbestos exposure. Survival related to tumor mesothelin expression, age, sex, histological type, location, asbestos exposure and pre-clinical SMRP was analysed. There was no significant association between biomarker levels and mesothelioma risk when analysed as continuous variables or as tertiles. Biomarker levels <10, 10-19 and >or=20 years before diagnosis were not significantly associated to mesothelioma risk. Mesothelin expressed in >50% of tumor cells was seen in 36 of 47 (77%) tumors. Mesothelin expression in <50% of tumor cells was a significant negative prognostic marker in all cases of malignant mesothelioma (median survival=6 months vs. 12 months, hazard ratio (HR)=2.49, 95%CI 1.17-5.27), and also when only epithelial mesothelioma was analysed (median=6 months vs. 14 months, HR=2.36, 95%CI 1.07-5.22). When adjusted for age and gender, the prognosis was still dismal, but non-significant (HR=1.85, 95%CI 0.85-4.05). High age (>65 years) was an independent negative prognostic factor that was related to both mesothelin expression and asbestos exposure. Mesothelioma of the epithelial type of the peritoneum had a significantly longer survival than epithelial type in pleura and was also related to mesothelin expression.

In plain English

This Norwegian nested case-control study linked the Janus Serum Bank to the Cancer Registry of Norway. It compared stored blood from 47 people who later developed malignant mesothelioma, taken 0.5 to 30 years before diagnosis, with blood from 141 matched controls. The authors measured three blood markers (SMRP, CA125 and CYFRA 21-1) and stained the cases' tumors for mesothelin. Asbestos exposure was estimated from census occupations; 26% of cases were classed as exposed, all men. No marker was significantly associated with later mesothelioma. In 36 of 47 tumors, more than 50% of cells expressed mesothelin. Cases with staining in 50% or fewer cells had shorter median survival (6 vs 12 months; hazard ratio 2.49, 95% CI 1.17 to 5.27). After adjusting for age and sex this difference was not statistically significant (1.85, 0.85 to 4.05). Peritoneal epithelial cases survived longer than pleural epithelial cases (median 45 vs 11 months). The authors concluded the markers cannot be recommended as screening tests, and named the small sample size as the main weakness.

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: Nested case-control study using stored pre-diagnostic serum (Janus Serum Bank linked with the Cancer Registry of Norway), with survival analysis of the cases
• Who was studied: 47 Norwegian malignant mesothelioma cases (7 women) with archival pre-diagnostic serum and histologically confirmed tumors, and 141 matched cancer-free controls (21 women); the time from blood sampling to diagnosis ranged from 0.5 to 30 years
• Exposure: Occupational asbestos exposure estimated from job titles in the 1960, 1970 and 1980 national censuses, classed as high, moderate or little/no exposure. No fiber types were specified. 26% of cases were classed as exposed, all men. The main measurements were serum SMRP, CA125 and CYFRA 21-1 and tumor mesothelin staining.
• Main results:
  • Serum SMRP, CA125 and CYFRA 21-1 levels were not associated with the odds of later mesothelioma, whether analysed as continuous or categorical variables, and adjustment for asbestos exposure or lag time did not essentially change this
  • Being recorded in an asbestos-exposed occupation at 2 to 3 censuses was associated with an odds ratio of mesothelioma of about 3 (2.96 in Table 2), 95% CI 0.84 to 10.5
  • Among the 47 cases, 36 (77%) had mesothelin expression in more than 50% of tumor cells
  • Among all cases, median survival was 12 months with mesothelin staining in more than 50% of tumor cells and 6 months with staining in 50% or fewer cells (n = 11). The crude hazard ratio was 2.49 (95% CI 1.17 to 5.27). Adjusted for age and sex it was 1.85 (95% CI 0.85 to 4.05), no longer statistically significant.
  • Among epithelial mesothelioma cases only, median survival was 14 months (more than 50% staining) vs 6 months (50% or fewer)
  • Cases with peritoneal epithelial tumors (n = 7) had a median survival of 45 months, compared with 11 months for pleural epithelial tumors (n = 33). The adjusted hazard ratio for pleural epithelial tumors was 7.03, 95% CI 1.93 to 25.62.
  • Age was a strong independent prognostic factor: cases aged 66 to 80 (n = 14) had a median survival of 3 months and a hazard ratio of 4.12 (95% CI 2.03 to 8.61) compared with cases aged 40 to 52
  • Asbestos exposure did not predict survival among the cases when adjusted for age
  • Tumor mesothelin expression was not correlated with pre-diagnostic serum SMRP levels
• The authors' conclusion: The authors concluded that SMRP, CA125 and CYFRA 21-1 were not elevated in serum 1 to 30 years before diagnosis and cannot be recommended as screening tests on these results. They said prospective studies in people at high risk are needed to reach a definite conclusion. They also concluded that tumors expressing mesothelin in more than 50% of cells had significantly longer survival when not adjusted for age and gender.
• Limitations the authors state:
  • Small sample size, because few cases had pre-diagnostic serum available
  • Old serum samples (mean storage time 24.5 years); SMRP and CYFRA 21-1 may be falsely elevated by long-term storage
  • Asbestos exposure data are expected to be misclassified, since occupation was recorded at only 1 to 3 time points and variation within occupations could not be accounted for
  • Cases were not a random selection of all diagnosed cases and were younger at diagnosis than the national mean
  • Sub-clinical cancer in controls cannot be ruled out, and non-malignant conditions may raise these markers

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, Malignant Mesothelioma, nested case-control study, Soluble Mesothelin-Related Peptides (SMRP), Disease Progression, Mesothelioma, Biomarker, Asbestos Exposure.

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)
• Mesothelin-family proteins and diagnosis of mesothelioma — B.W. Robinson, J. Creaney, et al. (2003)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• Diagnostic value of mesothelin in pleural fluids: comparison with CYFRA 21-1 and CEA — R. Filiberti, S. Parodi, et al. (2013)
• Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population — E.K. Park, P.S. Thomas, et al. (2010)
• Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2010)

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