Abstract 714: Survivin expression in patients with resected pancreatic adenocarcinoma

Abstract

Abstract Introduction: Pancreatic cancer remains highly refractory to treatment and biomarkers of treatment responsiveness are urgently needed. Survivin is an inhibitor of apoptosis and one such potential marker. Undetectable in most normal differentiated and non-proliferating tissues, it is highly expressed in cancer. We measured pancreatic cancer survivin expression and examined its association with differential treatment response. Methods: We constructed 4 pancreatic cancer tissue microarrays with 1mm duplicate cores using tumor samples from 88 resected pancreatic cancer patients at our center. They were then followed with 60 patients receiving chemotherapy or radiation, both as adjuvant therapy and also for palliative treatment upon recurrence. We measured survivin expression using highly quantitative automated immunofluorescence via AQUA R(HistoRx, Branford CT). Scores were individually reported for the nuclear, cytoplasmic and total cellular compartments, and validated by the pathologist. Results: Median survivin AQUA scores were: nuclear 5838 (range 2126-13728), cytoplasm 4177 (2173-9914) and total 4543 (2120-10344). Survivin expression was significantly higher in nodal specimens compared to primary tumor in nucleus (p=0.02), cytoplasm (p=0.006) and in total (p=0.0095). Higher cytoplasmic survivin correlated with higher grade (p=0.03), and primary tumor location in head compared to body or tail (p=0.03). There was a trend toward higher nuclear survivin in younger (p=0.08) and female patients (p=0.08). Disease-free survival (DFS) was significantly longer in patients with high compared to low nuclear survivin (p=0.048), using median as the cut-off. This effect was greater for patients treated with gemcitabine (p=0.0481) than those treated with 5-FU (p=0.0698) or radiation therapy (p=0.094). Overall survival for all patients was not different in the higher than median group compared to lower group patients (p=0.300). There was a trend toward longer overall survival (OS) for patients whose tumors had high nuclear survivin in those treated with fluorouracil (p=0.0856), gemcitabine (p=0.0868) or radiation therapy (p=0.0862). Discussion: Survivin expression is higher in nodal metastases than primary resected pancreatic cancer tumors and is associated with particular clinical and pathologic characteristics. High nuclear survivin expression is associated with longer DFS in patients with resected pancreatic cancer. This effect is most pronounced in patients treated with gemcitabine. Further examination of survivin in a larger series of pancreatic cancers is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 714. doi:1538-7445.AM2012-714