Does the expression of BCL2 have prognostic significance in malignant peritoneal mesothelioma?

Our plain-English summary of Does the expression of BCL2 have prognostic significance in malignant peritoneal mesothelioma?, by K. Pillai, M.H. Pourgholami, T.C. Chua, et al (American Journal of Cancer Research, 2013).

The study

• Authors: K. Pillai, M.H. Pourgholami, T.C. Chua, D.L. Morris
• Journal: American Journal of Cancer Research
• Published: 2013;3(3):312-22
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Unlabelled: Background Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneal membrane that is causally related to asbestos exposure. Survival after treatment is poor. Current therapy involving hyperthermic intraperitoneal chemotherapy has improved survival in selective patients. In the past, several prognostic factors have been identified in MPM patients and this has prompted the development of new therapies and patient management. Since BCL2, an antiapoptotic oncoprotein, is a favourable prognostic factor in breast cancer, we investigated to determine the significance of BCL2 in MPM. Materials and Methods Forty two archival patient tumour sections embedded in paraffin blocks were sectioned and subjected to immunohistochemistry to detect BCL2. The staining intensity and abundance was classified using standard procedures and classified into two groups (0-4 = low & 5-8 = high expression). The distribution of BCL2 groups was examined in the different clinicopathological categories to determine prognosis using Kaplan-Meier survival analysis.

Results: Univariate analysis revealed that in almost all clinicopathological categories, high BCL2 expression predisposed patients to a favourable prognosis. Independent of BCL2 expression, univariate analysis also showed that male gender, sarcomatoid histology, high PCI and age at diagnosis ≥ 60 years were associated poor prognosis. Multivariate analysis indicated that for all tumours, males and females, high BCL2 expression was associated with good prognosis. Further, independent of BCL2, age ≥ 60 years is an unfavourable prognostic factor.

Conclusion: Expression of BCL2 may serve to distinguish prognosis within the individual clinicopathological categories. BCL2 is also an independent variable in all tumours, males and females, with high expression being associated with good prognosis.

In plain English

This study examined tumour samples from 42 patients (20 males, 22 females, median age 57) with malignant peritoneal mesothelioma diagnosed at St George Hospital, Australia, from 1999 to December 2012. Archived tissue was stained for BCL2, a protein that blocks cell death. Samples scoring 0-4 counted as low expression and 5-8 as high. The article does not report the patients' asbestos exposure. Low BCL2 was found in 28 patients (66%), high in 14 (34%). Across all tumours, high expression was associated with better survival in the unadjusted analysis (p = 0.004) and in the adjusted analysis (hazard ratio 6.4, confidence interval 2.32 to 17.61). However, the adjusted table labels this ratio 'high versus low', which conflicts with that direction. The same association was seen in each sex. Of the other factors, only age 60 or older at diagnosis remained linked to poorer survival after adjustment. Its hazard ratio was 3.3 (p = 0.049), with a confidence interval of 1.4 to 16.4 in the text but 1.6 to 16.4 in the table. Several subgroup results were not statistically significant. The authors recommended routine BCL2 testing but called for a larger study. Other text and table numbers also disagree.

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 archived (formalin-fixed, paraffin-embedded) tumour samples. BCL2 was measured by immunohistochemistry, and survival was analysed with Kaplan-Meier, log-rank and Cox proportional hazards methods.
• Who was studied: 42 patients (20 males, 22 females; median age 57 years, range 23-69) diagnosed with malignant peritoneal mesothelioma at St George Hospital, Kogarah, NSW, Australia, from 1999 to December 2012.
• Exposure: No asbestos exposure was measured or reported for these patients. The factor studied was BCL2 protein expression in the tumour. Staining intensity (0-3) and the proportion of stained cells (0-5) were added together. A score of 4 or below counted as low expression and 5-8 as high expression.
• Main results:
  • Of the 42 patients, 28 (66%) had low BCL2 expression (group 1) and 14 (34%) had high expression (group 2).
  • In unadjusted (univariate) analysis, high BCL2 expression was associated with better survival in all tumours (Table 2: low vs high HR 6.0, 95% CI 2.23-16.44, p = 0.004), in males (p = 0.030) and in females (p = 0.001).
  • In unadjusted analysis, the BCL2 difference was not statistically significant in two subgroups:
• male patients with epithelial tumours (p = 0.257)
• patients aged 60 or older at diagnosis (HR 3.9, CI 0.52-30.18, p = 0.182)
  • Separately from BCL2, unadjusted analysis linked poorer survival to:
• male sex (p = 0.007)
• sarcomatoid histology (p = 0.001)
• PCI of 20 or more (p = 0.013)
• age at diagnosis of 60 or older (p = 0.001)
  • In adjusted (multivariate) analysis, the text reports high BCL2 expression as associated with better survival in all tumours: HR 6.4 (95% CI 2.32-17.61), p = 0.038. Table 3 labels this row 'High vs Low BCL2 Expression', while other BCL2 rows are labelled 'Low vs High'. The table label therefore conflicts with the direction the text reports.
  • In adjusted analysis, the BCL2 association held in each sex:
• males: HR 4.7 (CI 1.41-16.2), p = 0.038
• females: HR 7.3 (CI 1.72-38.6), p = 0.048
  • Among factors other than BCL2, only age at diagnosis of 60 years or older was an independent predictor of poorer survival in adjusted analysis: HR 3.3, p = 0.049. The confidence interval is 1.4-16.4 in the text but 1.6-16.4 in Table 3.
  • In adjusted analysis, PCI was not an independent predictor of survival. Per Table 3, male vs female sex, sarcomatoid vs epithelial histology, and the BCL2 results within the epithelial, PCI and under-60 subgroups were also not statistically significant.
• The authors' conclusion: The authors stated that high BCL2 expression is related to a survival advantage. They recommended routine BCL2 screening to determine patients' prognostic status, while noting that the study may need validation with a larger sample.
• Limitations the authors state:
  • Results for sarcomatoid tumours were not validated because there were too few of them (7).
  • The study may need further validation in a larger sample; the authors recommended a multi-institutional study.

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Neoplasm, Asbestos Exposure, HIPEC, Paraffin Block, Immunohistochemistry, Prognosis, Sarcomatoid.

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