University Hospitals of Cleveland, Cleveland, OH, USA.
Int J Gynecol Cancer. 2013 May;23(4):615-21. doi: 10.1097/IGC.0b013e31828b4eb5.
To evaluate pretherapy ribonucleotide reductase (RNR) expression and its effect on radiochemotherapeutic outcome in women with cervical cancer.
METHODS/MATERIALS: Pretherapy RNR M1, M2, and M2b immunohistochemistry was done on cervical cancer specimens retrieved from women treated on Radiation Therapy Oncology Group (RTOG) 0116 and 0128 clinical trials. Enrollees of RTOG 0116 (node-positive stages IA-IVA) received weekly cisplatin (40 mg/m(2)) with amifostine (500 mg) and extended-field radiation then brachytherapy (85 Gy). Enrollees of RTOG 0128 (node-positive or bulky ≥5 cm, stages IB-IIA or stages IIB-IVA) received cisplatin (75 mg/m(2)) on days 1, 23, and 43 and 5-FU (1 g/m(2) for 4 days) during pelvic radiation then brachytherapy (85 Gy), plus celecoxib (400 mg twice daily, day 1 through 1 year). Disease-free survival (DFS) was estimated univariately by the Kaplan-Meier method. Cox proportional hazards models evaluated the impact of RNR immunoreactivity on DFS.
Fifty-one tissue samples were analyzed: 13 from RTOG 0116 and 38 from RTOG 0128. M1, M2, and M2b overexpression (3+) frequencies were 2%, 80%, and 47%, respectively. Low-level (0-1+, n = 44/51) expression of the regulatory subunit M1 did not associate with DFS (P = 0.38). High (3+) M2 expression occurred in most (n = 41/51) but without impact alone on DFS (hazard ratio, 0.54; 95% confidence interval, 0.2-1.4; P = 0.20). After adjusting for M2b status, pelvic node-positive women had increased hazard for relapse or death (hazard ratio, 5.5; 95% confidence interval, 2.2-13.8; P = 0.0003).
These results suggest that RNR subunit expression may discriminate cervical cancer phenotype and radiochemotherapy outcome. Future RNR biomarker studies are warranted.
评估核糖核苷酸还原酶（RNR）在接受放化疗的宫颈癌患者中的表达及其对放化疗疗效的影响。
方法/材料：对来自接受放射治疗肿瘤学组（RTOG）0116 和 0128 临床试验的宫颈癌标本进行了 RNR M1、M2 和 M2b 的免疫组织化学检测。RTOG 0116 入组患者（淋巴结阳性ⅠA-IVA 期）接受每周顺铂（40mg/m²）联合氨磷汀（500mg）和外照射，然后行近距离放疗（85Gy）。RTOG 0128 入组患者（淋巴结阳性或肿瘤直径大于 5cm，IB-IIA 期或 IIB-IVA 期）接受顺铂（75mg/m²），于第 1、23 和 43 天以及第 1 天至 1 年期间每天 2 次给予塞来昔布（400mg）和氟尿嘧啶（1g/m²，连用 4 天），同时行盆腔放疗和近距离放疗（85Gy）。无病生存（DFS）采用 Kaplan-Meier 法进行单因素估计。Cox 比例风险模型评估了 RNR 免疫反应性对 DFS 的影响。
分析了 51 份组织样本：13 份来自 RTOG 0116，38 份来自 RTOG 0128。M1、M2 和 M2b 过表达（3+）的频率分别为 2%、80%和 47%。调节亚基 M1 的低水平（0-1+，n=44/51）表达与 DFS 无关（P=0.38）。高（3+）M2 表达发生在大多数患者（n=41/51）中，但单独对 DFS 无影响（风险比，0.54；95%置信区间，0.2-1.4；P=0.20）。在调整 M2b 状态后，盆腔淋巴结阳性的患者复发或死亡的风险增加（风险比，5.5；95%置信区间，2.2-13.8；P=0.0003）。
这些结果表明，RNR 亚基表达可能区分宫颈癌表型和放化疗疗效。需要进一步进行 RNR 生物标志物的研究。
