Departments of Radiation Oncology.
Alexandria Clinical Research Center.
Am J Clin Oncol. 2021 Feb 1;44(2):58-67. doi: 10.1097/COC.0000000000000781.
PURPOSE/OBJECTIVE: The objective of this study was to assess the association between pretreatment p53, hypoxia inducible factor 1a (HIF1a), Ki-67, carbonic anhydrase-9 (CA-9), and glucose transporter 1 (GLUT1) expression in locally advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), local-regional control (LC), and distant metastases-free survival (DMFS).
Twenty-eight patients treated definitively and consecutively for cervical cancer with CRT had p53, HIF1a, Ki-67, CA-9, and GLUT1 protein expression assessed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes. Outcomes were stratified by p53 (H-score: <15 vs. ≥15), HIF1a (H-score: <95 vs. ≥95), Ki-67 (labeling index <41% vs. ≥41%), CA-9 (H-score: <15 vs. ≥15), and GLUT1 (H-score: <175 vs. ≥175) expression. OS, PFS, LC, and DMFS rates were calculated using the Kaplan-Meier method, and differences between groups were evaluated by the log-rank test.
Notable clinical characteristics of the cohort included median age of 51 years (range: 32 to 74 y), FIGO stage IIB disease (57.2%), clinical node-negative disease (64.3%), squamous cell carcinoma (89.3%), and adenocarcinoma (10.7%). Treatment outcomes included 5-year OS (57.2%), PFS (48.1%), LC (72.1%), and DMFS (62.9%). For HIF1a H-score <95 and ≥95, the 5-year OS (52.0% and 68.4%, P=0.58), PFS (53.0% and 40.9%, P=0.75), LC (71.6% and 68.2%, P=0.92), and DMFS (59.7% and 52.0%, P=0.91) were not significantly different. For Ki-67 labeling index <41% and ≥41%, the 5-year OS (44.9% and 66.6%, P=0.35), PFS (38.9% and 55.4%, P=0.53), LC (57.7% and 85.7%, P=0.22), and DMFS (67.3% and 61.0%, P=0.94) were not significantly different. For CA-9 H-score <15 and ≥15, the 5-year OS (54.4% and 66.7%, P=0.39), PFS (57.3% and 40.0%, P=0.87), LC (70.0% and 70.0%, P=0.95), and DMFS (70.0% and 46.7%, P=0.94) were not significantly different. For GLUT1 H-score <175 and ≥175, the 5-year OS (43.6% and 43.6%, P=0.32), PFS (55.6% and 49.5%, P=0.72), LC (72.9% and 71.5%, P=0.97), and DMFS (62.5% and 59.6%, P=0.76) were not significantly different. For p53, H-score <15 and ≥15, the 5-year OS (62% and 53%), PFS (63% and 30.3%), LC (87.5% and 52%), and DMFS (79.6% and 41.6%).
In this study population, HIF1a, Ki-67, CA-9, and GLUT1 expression did not predict treatment response or outcomes in locally advanced cervical cancer patients treated definitively with CRT. There was a nonstatistically significant trend towards worse outcomes with p53 expression.
目的/目标：本研究的目的是评估在接受同步放化疗（CRT）治疗的局部晚期宫颈癌患者中，预处理 p53、缺氧诱导因子 1a（HIF1a）、Ki-67、碳酸酐酶 9（CA-9）和葡萄糖转运蛋白 1（GLUT1）表达与总生存（OS）、无进展生存（PFS）、局部区域控制（LC）和无远处转移生存（DMFS）等治疗结果之间的关联。
28 例接受 CRT 治疗的局部晚期宫颈癌患者的 p53、HIF1a、Ki-67、CA-9 和 GLUT1 蛋白表达情况由 3 位病理学家进行评估和半定量评分，评分过程中对治疗结果进行了盲法处理。根据 p53（H 评分：<15 与≥15）、HIF1a（H 评分：<95 与≥95）、Ki-67（标记指数<41%与≥41%）、CA-9（H 评分：<15 与≥15）和 GLUT1（H 评分：<175 与≥175）的表达情况对患者进行分层。使用 Kaplan-Meier 法计算 OS、PFS、LC 和 DMFS 率，并通过对数秩检验评估组间差异。
队列的显著临床特征包括中位年龄 51 岁（范围：32 至 74 岁）、FIGO 分期 IIB 疾病（57.2%）、临床淋巴结阴性疾病（64.3%）、鳞状细胞癌（89.3%）和腺癌（10.7%）。治疗结果包括 5 年 OS（57.2%）、PFS（48.1%）、LC（72.1%）和 DMFS（62.9%）。对于 HIF1a H 评分<95 和≥95，5 年 OS（52.0%和 68.4%，P=0.58）、PFS（53.0%和 40.9%，P=0.75）、LC（71.6%和 68.2%，P=0.92）和 DMFS（59.7%和 52.0%，P=0.91）均无显著差异。对于 Ki-67 标记指数<41%和≥41%，5 年 OS（44.9%和 66.6%，P=0.35）、PFS（38.9%和 55.4%，P=0.53）、LC（57.7%和 85.7%，P=0.22）和 DMFS（67.3%和 61.0%，P=0.94）均无显著差异。对于 CA-9 H 评分<15 和≥15，5 年 OS（54.4%和 66.7%，P=0.39）、PFS（57.3%和 40.0%，P=0.87）、LC（70.0%和 70.0%，P=0.95）和 DMFS（70.0%和 46.7%，P=0.94）均无显著差异。对于 GLUT1 H 评分<175 和≥175，5 年 OS（43.6%和 43.6%，P=0.32）、PFS（55.6%和 49.5%，P=0.72）、LC（72.9%和 71.5%，P=0.97）和 DMFS（62.5%和 59.6%，P=0.76）均无显著差异。对于 p53，H 评分<15 和≥15，5 年 OS（62%和 53%）、PFS（63%和 30.3%）、LC（87.5%和 52%）和 DMFS（79.6%和 41.6%）。
在本研究人群中，HIF1a、Ki-67、CA-9 和 GLUT1 表达与局部晚期宫颈癌患者接受 CRT 治疗后的治疗反应或结局无关。p53 表达与结局呈非统计学显著的负相关。
