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

Abstract

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.

Keywords: BCL2; peritoneal mesothelioma; prognosis; survival.

Figure 1

A shows the staining pattern in control slide with expression of BCL2 (brown stain). B, C, and D are staining pattern in three MPM patients. Patient B has higher intensity of staining, whilst patient C and D have a lower intensity of staining. A higher abundance of staining is shown in patience C, compared to patient B and D. For immunohistochemical staining, glass tissue mounted slides were deparaffinised in xylene and ethanol, microwave irradiated and treated with mouse monoclonal anti-BCL2 followed by rabbit ant-mouse secondary antibody (En Vision Method). Magnification is 20 x 0.45 (detail of method referenced earlier).

Figure 2

represents Kaplan-Meier Survival Curves, A for all tumours; B for males and C for Females. Low expression of BCL2 leads to poor survival.

Figure 3

represent Kaplan-Meier Survival Curves, A for all epithelial tumors; B & C for males and females; D & E for age at diagnosis < 60 and ≥ 60 years. Low BCL2 expression leads to poor survival.