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

Lung Cancer. Volume 50, Issue 2, November 2005, Pages 189-198. Received 24 January 2005; revised 20 May 2005; accepted 23 May 2005. Available online 25 July 2005. [Link]

Nurdan Kokturk^a, Pinar Firat^b, Hadi Akay^c, Cem Kadilar^d, Can Ozturk^a, Faruk Zorlu^e, Yucel Gungen^b and Salih Emri^f

^aGazi University School of Medicine, Department of Pulmonary Medicine, Ankara, Turkey
^bHacettepe University School of Medicine, Department of Pathology, Ankara, Turkey
^cAnkara University School of Medicine, Department of Thoracic Surgery, Ankara, Turkey
^dHacettepe University School of Medicine, Department of Statistics, Ankara, Turkey
^eHacettepe University School of Medicine, Department of Radiation Oncology, Ankara, Turkey
^fHacettepe University School of Medicine, Department of Pulmonary Medicine, Ankara, Turkey

Abstract

Summary: 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.

Keywords: Mesothelioma; Erionite; Asbestos; Apoptosis; Bax; Fas Ligand