γ-H2AX expression detected by immunohistochemistry correlates with prognosis in early operable non-small cell lung cancer
Authors Matthaios D, Foukas, Kefala M, Hountis P, Trypsianis, Panayiotides, Chatzaki, Pantelidaki E, Bouros, Karakitsos P, Kakolyris
Received 14 August 2012
Accepted for publication 14 September 2012
Published 30 October 2012 Volume 2012:5 Pages 309—314
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 5
Dimitrios Matthaios,1 Periklis G Foukas,2 Maria Kefala,2 Panagiotis Hountis,3 Grigorios Trypsianis,4 Ioannis G Panayiotides,2 Ekaterini Chatzaki,5 Ekaterini Pantelidaki,6 Demosthenes Bouros,7 Petros Karakitsos,8 Stylianos Kakolyris1
1Department of Oncology, Democritus University of Thrace, Alexandroupolis, Greece; 2Department of Pathology, Attikon University Hospital, Athens, Greece; 3Cardiac Surgery Department, Athens Naval and Veterans Hospital, Athens, Greece; 4Laboratory of Statistics, Democritus University of Thrace, Alexandroupolis, Greece; 5Laboratory of Pharmacology, Democritus University of Thrace, Alexandroupolis, Greece; 6Department of Pathology, Evaggelismos Hospital, Athens, Greece; 7Department of Pneumonology, Democritus University of Thrace, Alexandroupolis, Greece; 8Department of Cytopathology, Attikon University Hospital, Athens, Greece
Background: Phosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response. In the present study, we assessed the expression and prognostic significance of γ-H2AX in a cohort of 96 patients with operable non-small cell lung carcinoma.
Methods: Ninety-six paraffin-embedded specimens of non-small cell lung cancer patients were examined. All patients underwent radical thoracic surgery of primary tumor (lobectomy or pneumonectomy) and regional lymph node dissection. γ-H2AX expression was assessed by standard immunohistochemistry. Follow-up was available for all patients; mean duration of follow-up was 27.50 ± 14.07 months (range 0.2–57 months, median 24 months).
Results: Sixty-three patients (65.2%) died during the follow-up period. The mean survival time was 32.2 ± 1.9 months (95% confidence interval [CI]: 28.5–35.8 months; median 30.0 months); 1-, 2- and 3-year survival rates were 86.5% ± 3.5%, 57.3% ± 5.1%, and 37.1% ± 5.4%, respectively. Low γ-H2AX expression was associated with a significantly better survival as compared with those having high γ-H2AX expression (35.3 months for low γ-H2AX expression versus 23.2 months for high γ-H2AX expression, P = 0.009; hazard ratio [HR] 1.95, 95% CI: 1.15–3.30). Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained an independent prognostic factor of shorter overall survival (HR 2.15, 95% CI: 1.22–3.79, P = 0.026). A combined p53/ γ-H2AX analysis was performed, and we found that the p53 low/γ-H2AX low phenotype was associated with significantly better survival compared with all other phenotypes.
Conclusion: Our study is the first to demonstrate that expression of γ-H2AX detected by immunohistochemistry may represent an independent prognostic indicator of overall survival in patients with non-small cell lung cancer. Further studies are needed to confirm our results.
Keywords: H2AX, DNA damage response, non-small cell lung cancer, p53, prognosis