Calretinin but not caveolin-1 correlates with tumour histology and survival in malignant mesothelioma

Our plain-English summary of Calretinin but not caveolin-1 correlates with tumour histology and survival in malignant mesothelioma, by B. Thapa, M. Walkiewicz, C. Murone, et al (Pathology, 2016).

The study

• Authors: B. Thapa, M. Walkiewicz, C. Murone, K. Asadi, S. Deb, S. Barnett, S. Knight, P. Mitchell, D. Liew, D.N. Watkins, T. John
• Journal: Pathology
• Published: 2016;48(7):660-665
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) continues to be a disease with poor prognosis and limited treatment options. Calretinin and caveolin-1 expression by tumour in MM have recently been described to be associated with tumour histology, differentiation and consequently survival. In a large, well annotated cohort, we studied both of these biomarkers and explored their association with clinicopathological parameters and survival. A retrospective search of patients with MM who underwent surgery at the Austin Hospital in Melbourne, Australia, was conducted. Clinical history and outcome data were retrieved from patient records. Tissue microarrays (TMAs) were constructed and stained for calretinin and caveolin-1. 'H scores' were derived, taking intensity and distribution of staining, and the cohort was dichotomised using median values for both markers. In the 329 patients evaluated, median age was 67 years. Males outnumbered females by 5:1. Epithelioid histology 202/319 (62.9%) was the most common, followed by biphasic 72/319 (21.8%) and sarcomatoid 45/319 (13.6%); histology could not be confirmed in 10 patients. Calretinin expression was detected in 246 of the 324 (76%) evaluable patients and high expression was associated with epithelioid histology (p < 0.0001). Caveolin-1 was expressed in 298 (94%) of 317 evaluable patients which was much higher compared to its expression in a cohort of lung adenocarcinomas (8/58, 13.7%). However, no association with histology was found (p = 0.409). When taken as a continuous variable, calretinin expression was found to be an independent predictor of survival, alongside histology, neutrophil-lymphocyte ratio, weight loss and stage. No prognostic value was demonstrable for caveolin-1 expression and calretinin/caveolin-1 ratio. There was no relationship between calretinin and caveolin-1 expression. In MM, increased calretinin expression is associated with epithelioid histology and better survival. Caveolin-1 is a sensitive MM marker and is expressed in a high proportion of cases but lacks association with histology and survival.

Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

In plain English

This study looked back at 329 patients with confirmed malignant mesothelioma who had surgery at the Austin Hospital in Melbourne, Australia, between 1988 and 2014. The authors stained tumour samples for two proteins, calretinin and caveolin-1. Calretinin was found in 246 of 324 evaluable patients (76%), and higher levels were linked with the epithelioid tumour type. Caveolin-1 was found in 298 of 317 (94%) but was not linked with tumour type. By comparison, it was found in 8 of 58 (13.7%) lung adenocarcinomas. Median survival for the whole cohort was 12.5 months (95% CI 10.9 to 14.0). Measured as a continuous score, calretinin was linked with longer survival (hazard ratio 0.997; 95% CI 0.997 to 1.00), though not when patients were split at the median score. Caveolin-1 was not linked with survival. Higher caveolin-1 was associated with older age and with a history of asbestos exposure, findings the authors said need further validation. The authors concluded that calretinin, but not caveolin-1, relates to tumour type and survival. They noted sampling error from small tissue cores and varied treatments as limitations.

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 cohort study of surgical patients' records and archived tumour tissue, using tissue microarrays and immunohistochemistry
• Who was studied: Of 373 patients who had surgery for malignant mesothelioma at the Austin Hospital, Melbourne, Australia, between 1988 and 2014, 329 with confirmed malignant mesothelioma and usable tissue were studied. A separate set of 58 lung adenocarcinomas was stained for caveolin-1 for comparison.
• Exposure: The study measured tumour expression of calretinin and caveolin-1, not asbestos exposure. A history of asbestos exposure was recorded from patient records. The text says 26% had no definite history; Table 1 lists 239 (72.6%) with a definite history and 90 (27.3%) without.
• Main results:
  • Calretinin was detected in 246 of 324 evaluable patients (76%).
  • Calretinin was positive in 173 of 198 epithelioid (87.3%), 54 of 69 biphasic (78%) and 6 of 42 sarcomatoid (14.2%) mesotheliomas. A higher calretinin score was significantly associated with epithelioid histology (p less than 0.0001).
  • Caveolin-1 was detected in 298 of 317 evaluable patients (94%).
  • By histology, caveolin-1 was found in 177 of 193 epithelioid (91%), 66 of 68 biphasic (97%) and 41 of 42 sarcomatoid (97.6%) cases. There was no association with histology (p = 0.409).
  • Caveolin-1 was detected in 8 of 58 lung adenocarcinomas (13.7%), compared with 94% of mesotheliomas.
  • Median survival of the whole cohort was 12.5 months (95% CI 10.9 to 14.0).
  • In multivariate analysis, calretinin taken as a continuous score was significantly associated with improved overall survival (HR = 0.997; 95% CI 0.997 to 1.00; p = 0.009).
  • The calretinin survival association held only for the continuous score, not when patients were split at the median.
  • Caveolin-1 was not significantly associated with survival (HR = 1.001; 95% CI 0.98 to 1.002; p = 0.23).
  • Other predictors of better survival were absence of significant weight loss (HR = 0.64; 95% CI 0.47 to 0.87), early stage (HR = 0.28; 95% CI 0.15 to 0.55) and epithelioid histology (HR = 0.37; 95% CI 0.23 to 0.58). A high neutrophil-lymphocyte ratio predicted poorer survival (HR = 1.03; 95% CI 1.007 to 1.058).
  • Calretinin and caveolin-1 scores showed a weak negative correlation across the whole cohort (r = -0.14; p = 0.01).
  • Higher caveolin-1 expression was associated with older age at diagnosis (p = 0.04) and with a history of asbestos exposure (p = 0.02). Calretinin scores showed no significant correlation with factors including asbestos exposure.
• The authors' conclusion: The authors concluded that calretinin expression in malignant mesothelioma is related to histology and survival, while caveolin-1 is not. Because caveolin-1 is expressed in a large number of mesotheliomas, unlike in non-small cell lung cancer, they saw it as a potential diagnostic marker for telling mesothelioma apart from other tumours that spread to the pleura.
• Limitations the authors state:
  • Using tissue microarrays instead of full tissue sections is subject to sampling error.
  • The cohort was retrospective and the treatments patients received varied over the 26-year period.
  • The authors said the clinical relevance of the links between caveolin-1 and age and between caveolin-1 and asbestos exposure is not clear and that these findings warrant further validation.

Topics

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

Medical terms in this study, explained in our Lexicon: Calretinin, Histology, Mesothelioma, Prognosis, Biomarker, Epithelioid, Biphasic Mesothelioma, Sarcomatoid.

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• Value of calretinin immunostaining in diagnostic pathology: a review and update — N.G. Ordóñez (2014)
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