Abstract B32: Special AT-rich sequence-binding protein 1 (SATB1) is an independent prognostic marker of poor prognosis in operated pancreatic and pancreatobiliary type adenocarcinomas

Abstract

Abstract Background: Special AT-rich sequence-binding protein 1 (SATB1) is a global gene regulator that has been demonstrated to confer a more aggressive tumor phenotype and a shorter patient survival in several major cancer forms. The expression and prognostic significance of SATB1 in pancreatic, distal bile duct, ampullary or duodenal adenocarcinomas has however not yet been reported. Material and methods: A consecutive retrospective cohort of 175 patients with pancreatic and periampullary adenocarcinomas, operated with pancreaticoduodenectomy from January 1 2001 – December 31 2011, in the University hospitals of Lund and Malmö, Sweden, were followed up until December 31 2013. Microscopic slides were revised in a blinded manner and histopathological parameters relevant for classification and prognosis were recorded. Tissue microarrays were constructed from all primary tumors and 103 matched lymph node metastases. The expression of SATB1 was assessed by immunohistochemistry, and any intensity in more than 1% of cancer cells was considered a positive staining. Five-year overall survival was calculated and visualized using the Kaplan-Meier method and log rank analysis, stratified for tumor morphology and expression of SATB1. Cox regression models were used to estimate the impact of SATB1-expression on 5-year overall survival in multivariable analysis, adjusted for clinicopathological parameters. The Chi-square test and Fischer’s Exact test were used for calculations of correlations between SATB1-expression and other parameters. Results: SATB1-expression could be assessed in 107 pancreatobiliary type primary tumors (pancreatic, distal bile duct and ampullary origin) and in 61 intestinal type tumors (ampullary and duodenal origin). Median 5-year overall survival was 26.4 months in pancreatobiliary type adenocarcinomas and 53.3 months in intestinal type adenocarcinomas. There were 15% (16/107) SATB1-positive pancreatobiliary type adenocarcinomas and 25% (15/61) SATB1-positive intestinal type adenocarcinomas. Pancreatobiliary type SATB1-positive cases had a shorter median 5-year overall survival; median 14.6 months (interquartile range 8.9 – 24.7) vs. 27.5 months (interquartile range 15.8 – 46.3) compared to negative cases (p=0.014). The difference in 5-year overall survival remained significant in multivariable analysis (p=0.014) and the hazard ratio was 2.2 (95% CI 1.2 – 4.0) adjusted for T-stage, N-stage, tumor size, tumor grade, perineural growth, invasion in lymphatic vessels, invasion in blood vessels, growth in peripancreatic fat, involved margins, age and sex. Other independent parameters in pancreatobiliary type tumors were tumor grade, tumor size and invasion in blood vessels. SATB1-expression was correlated to invasion in blood vessels (p=0.009), but not to any other clinicopathological parameter. In intestinal type adenocarcinomas there was no correlation between primary tumor SATB1-positivity and overall survival. SATB1-expression could be assessed in metastases of 65 pancreatobiliary type adenocarcinomas and 24 intestinal type adenocarcinomas. There was a significant correlation between SATB1-positivity in primary tumors and metastases, but SATB1-expression in metastases was neither associated with clinicopathological parameters nor with survival. Conclusions: Our results show that SATB1-expression is an independent marker of poor prognosis in primary periampullary cancer of pancreatic and pancreatobiliary type and that SATB1-positivity is correlated to tumor invasion in blood vessels. This is the first report on the expression and prognostic significance of SATB1 in pancreatic cancer, distal bile duct cancer, ampullary cancer and duodenal cancer. Citation Format: Jacob Elebro, Karin Jirstrom. Special AT-rich sequence-binding protein 1 (SATB1) is an independent prognostic marker of poor prognosis in operated pancreatic and pancreatobiliary type adenocarcinomas. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B32.