Prognostic significance of Bax and Fas ligand in erionite and asbestos induced Turkish malignant pleural mesothelioma

Our plain-English summary of Prognostic significance of Bax and Fas ligand in erionite and asbestos induced Turkish malignant pleural mesothelioma, by N. Kokturk, P. Firat, H. Akay, et al (Lung Cancer, 2005).

The study

• Authors: N. Kokturk, P. Firat, H. Akay, C. Kadilar, C. Ozturk, F. Zorlu, Y. Gungen, S. Emri
• Journal: Lung Cancer
• Published: 2005;50(2):189-98
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Environmentally exposed erionite is a potent and unique inducer of malignant pleural mesothelioma (MPM) in Central Anatolia in Turkey. Previous studies have shown that erionite induced MPM has different biological behavior than asbestos induced MPM. Although impaired apoptosis has been implicated in tumor biology, the relationship between the type of environmental exposure and apoptosis has not yet been evaluated in MPM. The purpose of this study was to determine the expression of apoptosis regulating proteins and their prognostic significance in erionite and asbestos induced MPM. Thirty-five patients with MPM (16 erionite and 19 asbestos induced), and 17 patients with adenocarcinoma were comparatively evaluated. Expression of Bcl-2, Bax, Fas and Fas Ligand, were assessed by immunohistochemistry. Bcl-2 and Fas did not stain in almost all specimens. The staining extension of Bax was 13.75 +/- 19.27%, 5.89 +/- 14.51% and 7.38 +/- 14.53% for erionite and asbestos induced MPM and adenocarcinoma, respectively (p = 0.566). The staining extension of Fas Ligand was 26.87 +/- 31.87%, 46.10 +/- 37.30% and 26.47 +/- 23.23% for erionite and asbestos induced MPM, and adenocarcinoma, respectively (p = 0.123). Bax negative patients in erionite group had longer survival than Bax positive patients (18 months versus 14 months) (p = 0.06). Fas Ligand positive patients showed statistically better survival than Fas Ligand negative patients in all MPM group (15 months versus 12 months) (p = 0.05). Although all proteins expressed in similar extension in all samples, Bax staining displayed an inverse relation with survival in erionite group. This may implicate a difference in Bax functioning in erionite induced MPM. However, Fas Ligand may be functionally intact to reduce tumor survival.

In plain English

This Turkish study examined tumor tissue for four proteins involved in programmed cell death (apoptosis) in malignant pleural mesothelioma. It compared 16 patients from known erionite villages, whose mesothelioma was counted as erionite-induced, 19 from asbestos villages, and 17 with adenocarcinoma as controls. Bcl-2 and Fas were negative in most tissues. Average Bax and Fas Ligand staining did not differ significantly between groups. Median survival was 14 months in both mesothelioma groups. In the erionite group, the 10 patients without Bax staining had a median survival of 18 months, against 14 months for the 5 with Bax staining (p = 0.06), short of the study's 0.05 significance level. In a multivariate model, Bax negativity was independently linked to better survival in that group (p = 0.018). Among the 34 mesothelioma patients analysed for Fas Ligand, the 28 with staining had a median survival of 15 months, against 12 months for the 6 without (p = 0.05). The authors concluded that Bax expression was associated with poor prognosis only in erionite-induced mesothelioma. They noted small numbers, a wide confidence interval and staining-method limits.

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: Comparative immunohistochemistry study of tumor tissue sections, with survival analysis (Kaplan-Meier, log rank and Cox regression)
• Who was studied: 52 patients in Turkey: 16 with erionite-induced malignant pleural mesothelioma, 19 with asbestos-induced malignant pleural mesothelioma, and 17 with adenocarcinoma as controls. The study years are not given.
• Exposure: Environmental erionite or asbestos exposure, assigned by the patient's village of origin. Exposure was not measured, and asbestos fiber types are not specified.
• Main results:
  • Bcl-2 and Fas staining was negative in most tissues in all groups.
  • Mean Bax staining extension was 13.75 ± 19.27% in erionite-induced mesothelioma, 5.89 ± 14.51% in asbestos-induced mesothelioma and 7.38 ± 14.53% in adenocarcinoma (p = 0.566, not significant).
  • Mean Fas Ligand staining extension was 26.87 ± 31.87 in erionite-induced mesothelioma, 46.10 ± 37.30 in asbestos-induced mesothelioma and 26.47 ± 23.23 in adenocarcinoma (p = 0.123, not significant).
  • Median survival was 14 months (95% CI 12 to 16) in the erionite group and 14 months (95% CI 10 to 18) in the asbestos group (p = 0.47).
  • In the erionite group, Bax-negative patients (n = 10) had a median survival of 18 months (95% CI 12 to 24). Bax-positive patients (n = 5) had 14 months (95% CI 5 to 23) (p = 0.06).
  • The study counted p values of 0.05 or less as statistically significant, so the Bax survival comparison in the erionite group (p = 0.06) was above this threshold.
  • In the asbestos group, median survival was 15 months for Bax-negative patients and 14 months for Bax-positive patients (p = 0.34).
  • Among the 34 mesothelioma patients in this analysis, Fas Ligand-positive patients (n = 28) had a median survival of 15 months (95% CI 11 to 19). Fas Ligand-negative patients (n = 6) had 12 months (95% CI 0 to 25) (p = 0.05). The authors described this as statistically better survival.
  • In Cox regression for the erionite group, age under 50 (OR 6.52, 95% CI 1.01 to 42.17, p = 0.049) and Bax negativity (OR 18.83, p = 0.018) were each independently associated with better survival.
  • In Cox regression for all mesothelioma patients, Fas Ligand-positive patients had better survival (OR 3.12, 95% CI 0.99 to 9.79, p = 0.051).
• The authors' conclusion: The authors concluded that Bax expression was associated with poor prognosis only in erionite-induced mesothelioma, which may imply a difference in tumor behavior between erionite- and asbestos-induced disease. They also concluded that increased Fas Ligand expression may be associated with better survival across all mesothelioma patients.
• Limitations the authors state:
  • The sample size was too small for subgroup analyses.
  • The wide confidence interval weakened the Bax finding in the erionite group.
  • Immunohistochemistry has methodological limitations that must be kept in mind when interpreting the findings.
  • Other prognostic factors that this study could not detect may have contributed to the difference.

Topics

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

Medical terms in this study, explained in our Lexicon: erionite, Pleural Mesothelioma, Apoptosis, Environmental Exposure, Adenocarcinoma, Immunohistochemistry.

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