Yang Shih-Hung, Lee Jen-Chieh, Guo Jhe-Cyuan, Kuo Sung-Hsin, Tien Yu-Wen, Kuo Ting-Chun, Cheng Ann-Lii, Yeh Kun-Huei
Departments of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
PLoS One. 2017 Jul 5;12(7):e0180628. doi: 10.1371/journal.pone.0180628. eCollection 2017.
This study evaluated the prognostic roles of murine double minute 2 (MDM2) and p53 in pancreatic cancer patients treated with gemcitabine-based chemotherapy. A total of 137 advanced or recurrent adenocarcinoma patients who were treated with gemcitabine-based palliative chemotherapy were reviewed, selected from 957 patients with pancreatic malignancy between 2008 and 2013 at our hospital. Immunohistochemical staining for MDM2 and p53 with formalin-fixed, paraffin-embedded tumor tissues was independently reviewed. Nuclear or cytoplasmic expression of MDM2 and p53 was found in tumor cells of 30 (21.9%) and 71 (51.8%) patients, respectively. Patients with MDM2 expression had shorter median overall survival (OS) (3.7 vs 5.8 mo; P = .048) and median progression-free survival (PFS) (1.5 vs 2.5 mo; P < .001); by contrast, p53 expression was not correlated with OS or PFS. In the multivariate analysis, MDM2 expression (hazard ratio = 1.731; P = .025) was an independent and unfavorable prognostic factor of OS. Additionally, MDM2 expression was significantly associated with progressive disease (PD) and death (P = .015) following first-line gemcitabine-based therapy. In advanced pancreatic cancer patients, MDM2 expression is associated with shorter OS and PFS after gemcitabine-based chemotherapy.
本研究评估了鼠双微体2(MDM2)和p53在接受吉西他滨为主的化疗的胰腺癌患者中的预后作用。我们回顾了2008年至2013年间我院957例胰腺恶性肿瘤患者中,共137例接受吉西他滨为主的姑息化疗的晚期或复发性腺癌患者。对福尔马林固定、石蜡包埋的肿瘤组织进行MDM2和p53的免疫组织化学染色,并进行独立评估。分别在30例(21.9%)和71例(51.8%)患者的肿瘤细胞中发现了MDM2和p53的核或细胞质表达。MDM2表达阳性的患者中位总生存期(OS)较短(3.7个月对5.8个月;P = 0.048),中位无进展生存期(PFS)也较短(1.5个月对2.5个月;P < 0.001);相比之下,p53表达与OS或PFS均无相关性。多因素分析显示,MDM2表达(风险比 = 1.731;P = 0.025)是OS的独立不良预后因素。此外,MDM2表达与一线吉西他滨为主的治疗后的疾病进展(PD)和死亡显著相关(P = 0.015)。在晚期胰腺癌患者中,MDM2表达与吉西他滨为主的化疗后的OS和PFS缩短相关。