ATM and p53 combined analysis predicts survival in glioblastoma multiforme patients: A clinicopathologic study. Issue 6 (22nd February 2018)

• Record Type: Journal Article
• Authors: Romano, Francesco Jacopo; Guadagno, Elia; Solari, Domenico; Borrelli, Giorgio; Pignatiello, Sara; Cappabianca, Paolo; Del Basso De Caro, Marialaura
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 6(2018)
• Page Start: 4867
• Page End: 4877
• Publication Date: 2018-02-22
• Subjects: ATM -- DNA repair -- glioblastoma -- homologous recombination -- ionizing radiations -- non‐oncogene addiction -- p53; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26699
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Glioblastoma is one of the most malignant cancers, with a distinguishing dismal prognosis: surgery followed by chemo‐ and radiotherapy represents the current standard of care, and chemo‐ and radioresistance underlie disease recurrence and short overall survival of patients suffering from this malignancy. ATM is a kinase activated by autophosphorylation upon DNA doublestrand breaks arising from errors during replication, byproducts of metabolism, chemotherapy or ionizing radiations; TP53 is one of the most popular tumor suppressor, with a preeminent role in DNA damage response and repair. To study the effects of the immunohistochemical expression of p‐ATM and p53 in glioblastoma patients, 21 cases were retrospectively examined. In normal brain tissue, p‐ATM was expressed only in neurons; conversely, in tumors cells, the protein showed a variable cytoplasmic expression (score: +, ++, +++), with being completely undetectable in three cases. Statistical analysis revealed that high p‐ATM score (++/+++) strongly correlated to shorter survival ( P = 0.022). No difference in overall survival was registered between p53 normally expressed (NE) and overexpressed (OE) glioblastoma patients ( P = 0.669). Survival analysis performed on the results from combined assessment of the two proteins showed that patients with NE p53 /low pATM score had longer overall survival than the NE p53/ high pATM score counterpart. Cox‐regression analysis confirmed this finding (HR = 0.025; CI 95% = 0.002–0.284; P = 0.003). Our study outlined the immunohistochemical expression of p‐ATM/p53 in glioblastomas and provided data on their possible prognostic/predictive of response role. A " non‐oncogene addiction " to ATM for NEp53 glioblastoma could be postulated, strengthening the rationale for development of ATM inhibiting drugs. Abstract : High phosphorylated ATM strongly correlated to shorter survival ( P = 0.022). No difference in overall survival was registered between p53 normally expressed (NE) and overexpressed (OE) glioblastoma patients ( P = 0.669). Combined assessment of the two proteins showed that patients with NE p53 /low pATM score had longer overall survival than the NE p53/ high pATM score counterpart. Cox‐regression analysis confirmed this finding (HR = 0.025; P = 0.003). A "non‐oncogene addiction" to ATM for NEp53 glioblastoma could be postulated, strengthening the rationale for development of ATM inhibiting drugs.