Frischknecht Lukas, Meerang Mayura, Soltermann Alex, Stahel Rolf, Moch Holger, Seifert Burkhardt, Weder Walter, Opitz Isabelle
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
J Thorac Cardiovasc Surg. 2015 Jun;149(6):1539-46.e1. doi: 10.1016/j.jtcvs.2015.01.065. Epub 2015 Feb 12.
Survival and response to platinum-based induction chemotherapy are heterogeneous among patients with malignant pleural mesothelioma. The aim of the present study was to assess the prognostic role of DNA repair markers, such as excision repair cross-complementation group 1 and ribonucleotide reductase M1, in multimodally treated patients with malignant pleural mesothelioma.
Tumor tissue of a malignant pleural mesothelioma cohort (n = 107) treated with platinum/gemcitabine (n = 46) or platinum/pemetrexed (n = 61) induction chemotherapy followed by extrapleural pneumonectomy was assembled on a tissue microarray. Immunohistochemical expression of excision repair cross-complementation group 1 (nuclear) and ribonucleotide reductase M1 (nuclear and cytoplasmic) was assessed for its prognostic impact (association with overall survival or freedom from recurrence).
Patients with high nuclear ribonucleotide reductase M1 expression before chemotherapy showed significantly longer freedom from recurrence (P = .03). When specifically analyzed in the subgroup of patients receiving platinum/gemcitabine followed by extrapleural pneumonectomy, high nuclear ribonucleotide reductase M1 was associated with prolonged freedom from recurrence (P = .03) and overall survival (P = .02). Low excision repair cross-complementation group 1 expression in prechemotherapy tumor tissues was associated with significantly longer freedom from recurrence (P = .04). Nuclear ribonucleotide reductase M1 and excision repair cross-complementation group 1 were independent prognosticators of freedom from recurrence in addition to pT stage in multivariate analysis.
In the present study, nuclear ribonucleotide reductase M1 and excision repair cross-complementation group 1 expression were identified as independent prognosticators for freedom from recurrence of malignant pleural mesothelioma in patients undergoing induction chemotherapy followed by extrapleural pneumonectomy.
在恶性胸膜间皮瘤患者中，铂类诱导化疗后的生存率和反应存在异质性。本研究的目的是评估DNA修复标志物，如切除修复交叉互补组1（excision repair cross-complementation group 1，ERCC1）和核糖核苷酸还原酶M1（ribonucleotide reductase M1，RRRM1），在接受多模式治疗的恶性胸膜间皮瘤患者中的预后作用。
将接受铂类/吉西他滨（n = 46）或铂类/培美曲塞（n = 61）诱导化疗后行胸膜外全肺切除术的恶性胸膜间皮瘤队列（n = 107）的肿瘤组织制成组织芯片。评估ERCC1（细胞核）和RRRM1（细胞核和细胞质）的免疫组化表达对预后的影响（与总生存期或无复发生存期的相关性）。
化疗前RRRM1细胞核高表达的患者无复发生存期明显更长（P = 0.03）。在接受铂类/吉西他滨诱导化疗后行胸膜外全肺切除术的亚组患者中进行特异性分析时，RRRM1细胞核高表达与无复发生存期延长（P = 0.03）和总生存期延长（P = 0.02）相关。化疗前肿瘤组织中ERCC1低表达与无复发生存期明显更长相关（P = 0.04）。在多变量分析中，除了pT分期外，RRRM1细胞核和ERCC1是无复发生存期的独立预后因素。
在本研究中，RRRM1细胞核和ERCC1表达被确定为接受诱导化疗后行胸膜外全肺切除术的恶性胸膜间皮瘤患者无复发生存期的独立预后因素。
