γ-H2AX expression detected by immunohistochemistry correlates with prognosis in early operable non-small cell lung cancer.
γ-H2AX expression detected by immunohistochemistry correlates with prognosis in early operable non-small cell lung cancer.
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DOI：
10.2147/ott.s36995
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发表时间：
2012
影响因子：
4
通讯作者：
Kakolyris S
中科院分区：
文献类型：
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作者：
Matthaios D;Foukas PG;Kefala M;Hountis P;Trypsianis G;Panayiotides IG;Chatzaki E;Pantelidaki E;Bouros D;Karakitsos P;Kakolyris S
H2 AX组蛋白的磷酸化是DNA双链断裂和由此产生的DNA损伤反应的早期指标。在本研究中，我们评估了96例可手术非小细胞肺癌患者中γ-H2 AX的表达及其预后意义。对96例非小细胞肺癌患者的石蜡包埋标本进行了检查。所有患者均接受了原发肿瘤根治性手术（肺叶或全肺切除术）和区域淋巴结清扫术。通过标准免疫组织化学评估γ-H2 AX表达。对所有患者进行了随访;平均随访持续时间为27.50 ± 14.07个月（范围0.2-57个月，中位时间24个月）。63例患者（65.2%）在随访期间死亡。平均生存时间为32.2 ± 1.9个月（95%置信区间[CI]：28.5-35.8个月;中位数30.0个月）; 1年、2年和3年生存率分别为86.5% ± 3.5%、57.3% ± 5.1%和37.1% ± 5.4%。与γ-H2 AX高表达者相比，γ-H2 AX低表达者的生存期显著更好（γ-H2 AX低表达者为35.3个月，γ-H2 AX高表达者为23.2个月，P = 0.009;风险比[HR] 1.95，95%CI：1.15-3.30）。多因素考克斯比例风险回归分析显示，γ-H2 AX高表达仍是总生存期短的独立预后因素（HR 2.15，95%CI：1.22-3.79，P = 0.026）。进行了组合p53/γ-H2 AX分析，我们发现与所有其他表型相比，p53低/γ-H2 AX低表型与显著更好的存活相关。我们的研究首次证明免疫组化检测的γ-H2 AX表达可能代表非小细胞肺癌患者总生存期的独立预后指标。需要进一步的研究来证实我们的结果。
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. 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). 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. 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.