Low calretinin expression and high neutrophil-to-lymphocyte ratio are poor prognostic factors in patients with malignant mesothelioma undergoing extrapleural pneumonectomy

Our plain-English summary of Low calretinin expression and high neutrophil-to-lymphocyte ratio are poor prognostic factors in patients with malignant mesothelioma undergoing extrapleural pneumonectomy, by S.C. Kao, S. Klebe, D.W. Henderson, et al (Journal of Thoracic Oncology, 2011).

The study

• Authors: S.C. Kao, S. Klebe, D.W. Henderson, G. Reid, M. Chatfield, N.J. Armstrong, T.D. Yan, J. Vardy, S. Clarke, N. van Zandwijk, B. McCaughan
• Journal: Journal of Thoracic Oncology
• Published: 2011;6(11):1923-9
• Cited by: 74 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Survival after extrapleural pneumonectomy (EPP) is variable in patients with malignant pleural mesothelioma (MPM), and there are no validated prognostic factors that could be used preoperatively. We investigated the calretinin and D2-40 expression and the neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation as potential preoperative prognostic factors.

Methods: Consecutive patients who underwent EPP were included in this retrospective study. Potential prognostic factors such as age, gender, histological subtype, baseline laboratory parameters including NLR, and immunohistochemical staining for calretinin and D2-40 were evaluated. Overall survival (OS) from the date of surgery was determined by the Kaplan-Meier method. The prognostic value of the variables was examined using Cox regression, and significant factors (p < 0.05) were entered into a multivariate model to determine their independent effect.

Results: A total of 85 patients were included: median age 58 years; 80% men; 77% epithelial and 23% biphasic MPM. The median OS was 19.7 months. The following variables were predictive of longer OS: female gender (p = 0.02), epithelial subtype (p = 0.04), low NLR (p < 0.01), and high calretinin score (p < 0.001). In a multivariate analysis, only NLR ≥3 (hazard ratio 1.79; 95% confidence interval: 1.04-3.07; p = 0.04) and calretinin score ≤33 versus more than 67% (hazard ratio 4.72; 95% confidence interval: 1.97-11.32; p < 0.01) remained independent predictors. The addition of calretinin score increased the explained variation by 10.1%.

Conclusions: Both low calretinin expression and high NLR were independently associated with poor prognosis in patients with MPM undergoing EPP, and the calretinin score seemed to improve the accuracy of the prognostic model.

In plain English

This retrospective study looked at 85 consecutive patients with malignant pleural mesothelioma who had extrapleural pneumonectomy at two Sydney hospitals from 1994 to November 2009. The authors tested whether survival was predicted by the neutrophil-to-lymphocyte ratio (NLR, a blood measure of body-wide inflammation taken the day before surgery) and by the percentage of tumor cells staining for calretinin and D2-40. The study did not examine asbestos exposure. Median survival after surgery was 19.7 months (95% confidence interval 13.8–25.6 months). The authors used a model that included both NLR and calretinin score, plus age, gender and tumor subtype. In it, an NLR of 3 or more had a hazard ratio for death of 1.79 (95% confidence interval 1.04–3.07) compared with an NLR below 3. In the same model, calretinin in 33% of cells or fewer had a hazard ratio of 4.72 (1.97–11.32) compared with above 67%. Median survival was 35.8 months with calretinin above 67% and 6.9 months at 33% or below. The authors concluded that low calretinin and high NLR were independently associated with poor prognosis. They noted the study was retrospective, included no sarcomatoid cases and needs validation.

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 study of prognostic factors (survival analysis using Kaplan-Meier curves and Cox regression) in a surgical case series
• Who was studied: 85 consecutive patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP) at Royal Prince Alfred and Strathfield Private Hospitals, Sydney, Australia, from 1994 to November 2009. Median age was 58 years and 80% were men. 65 had epithelial and 20 had biphasic mesothelioma. Archival tissue was available for 80 patients, and 19 had chemotherapy before surgery.
• Exposure: Asbestos exposure was not studied. The factors examined were: the percentage of tumor cells labeled for calretinin and for D2-40 on tissue from the operation; the preoperative blood neutrophil-to-lymphocyte ratio; hemoglobin, platelet count and white cell count; and age, gender and histological subtype.
• Main results:
  • Median overall survival from the date of surgery for the whole cohort was 19.7 months (95% confidence interval 13.8–25.6 months).
  • NLR and calretinin score were converted to categories. Both remained significant in a multivariate model that contained both of them together with age, gender and histological subtype. For NLR of 3 or more versus below 3, the hazard ratio was 1.79 (95% CI 1.04–3.07). For calretinin of 33% or less versus more than 67%, the hazard ratio was 4.72 (95% CI 1.97–11.32). For calretinin of 34–67% versus more than 67%, the hazard ratio was 1.57 (95% CI 0.83–2.97, p 0.17).
  • Median overall survival was 26.7 months for patients with NLR less than 3 and 12.6 months for those with NLR of 3 or more.
  • Median overall survival by calretinin score was 35.8 months for scores above 67%, 14.5 months for scores of 34 to 67%, and 6.9 months for scores of 33% or less.
  • Combining NLR and calretinin into three categories gave median overall survival of 48.7 months for category 1, 15.9 months for category 2 and 6.4 months for category 3.
  • Adding calretinin score to age, gender and subtype increased the explained variation in survival by 10.1%. Adding NLR had only a minor effect on predictive accuracy.
  • Higher NLR was correlated with more advanced pathological stage (Spearman correlation 0.25).
• The authors' conclusion: The authors concluded that both low calretinin expression and high NLR were independently associated with poor prognosis in patients with malignant pleural mesothelioma undergoing EPP. They also concluded that the extent of calretinin labeling seems to be a useful factor to consider before surgery.
• Limitations the authors state:
  • The study was retrospective and shares the problems of retrospective analysis.
  • There were no patients with the sarcomatoid subtype in the series.
  • Only patients eligible for EPP were studied, so the results are less generalizable to all mesothelioma patients.
  • The results need validation in an independent series of patients, preferably done prospectively.
  • Even together with histological subtype, age and gender, calretinin score and NLR explained only 16.8% of the variation in survival.

Topics

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

Medical terms in this study, explained in our Lexicon: Calretinin, Malignant Mesothelioma, Extrapleural Pneumonectomy (EPP), Pleural Mesothelioma, Podoplanin (D2-40), Inflammation, Histological Subtype, Immunohistochemistry.

Related studies

• High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy — S.C. Kao, N. Pavlakis, et al. (2010)
• Malignant pleural mesothelioma: clinical experience and prognostic value of derived neutrophil-to-lymphocyte ratio and PD-L1 expression — L. Gutierrez-Sainz, P. Cruz, et al. (2021)
• Existing models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma — T.M. Meniawy, J. Creaney, et al. (2013)
• Comment on 'Existing prognostic models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma' — S.C. Kao, N. van Zandwijk, et al. (2014)
• Relation between neutrophil/lymphocyte ratio and primary tumor metabolic activity in patients with malign pleural mesothelioma — B.A. Özyürek, Ö. Özmen, et al. (2018)
• Response to comment on 'Existing prognostic models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma' — T.M. Meniawy, J. Creaney, et al. (2014)

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