The prognostic role of Beclin 1 protein expression in high-grade gliomas

• Published in: Autophagy Vol. 5; no. 7; pp. 930 - 936
• Main Authors: Pirtoli, Luigi, Cevenini, Gabriele, Tini, Paolo, Vannini, Marta, Oliveri, Giuseppe, Marsili, Stefania, Mourmouras, Vasileios, Rubino, Giovanni, Miracco, Clelia
• Format: Journal Article
• Language: English
• Published: United States 01.10.2009
• Subjects: Antineoplastic Agents, Alkylating - therapeutic use; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Autophagy - physiology; Beclin-1; Binding; Biology; Biomarkers, Tumor - metabolism; Bioscience; Brain Neoplasms - diagnosis; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain Neoplasms - therapy; Calcium; Cancer; Cell; Cycle; Dacarbazine - analogs & derivatives; Dacarbazine - therapeutic use; DNA Modification Methylases - genetics; DNA Modification Methylases - metabolism; DNA Repair Enzymes - genetics; DNA Repair Enzymes - metabolism; Glioma - diagnosis; Glioma - metabolism; Glioma - pathology; Glioma - therapy; Humans; In Situ Nick-End Labeling; Landes; Membrane Proteins - genetics; Membrane Proteins - metabolism; Middle Aged; Organogenesis; Prognosis; Proteins; Survival Analysis; Temozolomide; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 1554-8627; 1554-8635
• DOI: 10.4161/auto.5.7.9227

High Grade Gliomas (HGG) have a poor outcome, however, prognostic sub-groups of patients may be individuated by some clinico-biological parameters. It was recently demonstrated that the main response of HGG to therapy is autophagic death. Autophagy is involved in tumor suppression, and is defective in HGG, in which we previously found an underexpression of beclin 1 autophagic gene protein product. Underexpression of Beclin 1 protein has been correlated to poor patient outcome in other tumor types. In this paper, the prognostic role of beclin 1 expression in HGG patients was investigated. We firstly evaluated the tumor cell cytoplasmic expression of Beclin 1 protein (BPCE), in a sample of 76 HGG by immunohistochemistry, and compared it with cell proliferation and apoptosis. We found high BPCE score positively correlated with apoptosis, and negatively with cell proliferation (p < 0,05). We then correlated BPCE score with survival and other prognostic parameters (histological grading , MGMT gene methylation status, age, patient performance status according to the Karnofski classification (KPS), extent of surgery, radiation therapy (RT) modality, temozolomide chemotherapy (TMZ CHT), and optimal/suboptimal post-surgical treatment). Forty-seven (61.8%) and twenty-nine (38.2%) patients showed high and low BPCE scores, respectively. BPCE showed statistically significant correlations with survival both at the univariate (p = 0.03) and multivariate analysis (p = 0.037). High BPCE was also positively correlated  with high KPS values (p = 0.023), and with the accomplishment of an optimal post-operative therapy (p = 0.037). Furthermore, among patients showing a MGMT methylated gene, survival was significantly higher in cases with a higher BPCE score. BPCE score might be added to pathological evaluation of HGG for prognostic purposes.