Association of MDM2 expression with shorter progression-free survival and overall survival in patients with advanced pancreatic cancer treated with gemcitabine-based chemotherapy

<div><p>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; <i>P</i> = .048) and median progression-free survival (PFS) (1.5 vs 2.5 mo; <i>P</i> < .001); by contrast, p53 expression was not correlated with OS or PFS. In the multivariate analysis, MDM2 expression (hazard ratio = 1.731; <i>P</i> = .025) was an independent and unfavorable prognostic factor of OS. Additionally, MDM2 expression was significantly associated with progressive disease (PD) and death (<i>P</i> = .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.</p></div

Survival curves in patients stratified with MDM2 and p53.

<p>The OS curves stratified with (A) MDM2 expression, (B) p53 expression, and (C) MDM2 and p53 statuses were demonstrated. The dots represented censored observation. The OS was worse in patients with MDM2+ IHC staining (<i>P</i> = .048). The OS did not differ significantly between p53+ and p53- patients (<i>P</i> = .192). After stratification of MDM2 and p53 status, patients with MDM2+/p53- staining had the shortest OS (<i>P</i> = .003).</p

Patient characteristics.

<p>Patient characteristics.</p

Multivariate analysis for OS.

<p>Multivariate analysis for OS.</p

MDM2 and p53 status versus chemotherapy response and outcome.

<p>MDM2 and p53 status versus chemotherapy response and outcome.</p

Representative cases of IHC expression (magnification 400X).

<p>Cases of IHC expression with (A) MDM2+, (B) MDM2-, (C) p53+, and (D) p53- were demonstrated. The positive staining was predominantly nuclear for both MDM2 and p53.</p