Prognostic and treatment predictive significance of SATB1 and SATB2 expression in pancreatic and periampullary adenocarcinoma

Abstract

BackgroundPancreatic cancer and other pancreaticobiliary type periampullary adenocarcinomas have a dismal prognosis even after resection and neoadjuvant chemotherapy. Intestinal type periampullary adenocarcinomas generally have a better prognosis, but little is known on optimal neoadjuvant and adjuvant treatment. New prognostic and treatment predictive biomarkers are needed for improved treatment stratification of patients with both types of periampullary adenocarcinoma. Expression of the Special AT-rich sequence-binding protein 1 (SATB1) has been demonstrated to confer a worse prognosis in several tumour types, whereas its close homologue SATB2 is a proposed diagnostic and favourable prognostic marker for colorectal cancer. The prognostic value of SATB1 and SATB2 expression in periampullary adenocarcinoma has not yet been described.MethodsImmunohistochemical expression of SATB1 and SATB2 was analysed in tissue microarrays with primary tumours and a subset of paired lymph node metastases from 175 patients operated with pancreaticoduodenectomy for periampullary adenocarcinoma. Kaplan-Meier and Cox regression analysis were applied to explore the impact of SATB1 and SATB2 expression on recurrence free survival (RFS) and overall survival (OS).ResultsPositive expression of SATB1 was denoted in 16/106 primary pancreatobiliary type tumours and 11/65 metastases, and in 15/63 primary intestinal type tumours and 4/26 metastases, respectively. Expression of SATB1 was an independent predictor of a significantly shorter RFS and OS in pancreatobiliary type, but not in intestinal type adenocarcinomas. Moreover, SATB1 expression predicted an improved response to adjuvant chemotherapy in both tumour types. SATB2-expression was seen in 3/107 pancreatobiliary type primary tumours, and in 8/61 intestinal type primary tumours. The small number of cases with positive SATB2 expression did not allow for any firm conclusions on its prognostic value.ConclusionsThese findings demonstrate the potential utility of SATB1 as a prognostic and predictive biomarker for chemotherapy response in both intestinal type and pancreatobiliary type periampullary adenocarcinomas, including pancreatic cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0289-8) contains supplementary material, which is available to authorized users.

SATB2 targeted by methylated miR‐34c‐5p suppresses proliferation and metastasis attenuating the epithelial‐mesenchymal transition in colorectal cancer

“…As an exceptional example of pancreatic adenocarcinoma, SATB2 was reported to be unassociated with the overall prognosis of patients with pancreatic adenocarcinoma. 26 The discrepancy may be mainly owing to the fact that the varying cutoff values were adopted between our study and Elebro et al's when immunoscoring the positive expression of STAB2 on sections and when stratifying the subcohorts based on the intensity of immunostaining in the analysis of overall survival.…”

Role of conventional immunomarkers, HNF4‐α and SATB2, in the differential diagnosis of pulmonary and colorectal adenocarcinomas

“…In addition to colorectal cancer, SATB2 expression has also been described recently in other tumours, including carcinomas of the gastrointestinal tract such as small intestinal carcinoma, appendical mucinous neoplasm, pancreatic adenocarcinoma and oesophageal squamous cell carcinoma, as well as neoplasms of neuroectodermal and mesenchymal origin; for example, Merkel cell carcinoma, neuroendocrine tumours and osteosarcoma . However, as > 85% of CRC were SATB2‐positive in two large studies comprising > 1800 and > 100 CRC cases in total, this marker has been advocated to determine colorectal origin .…”

Pilot study special AT-rich sequence-binding protein 1 investigating as a potential biomarker for esophageal squamous cell carcinoma

“…SATB1 binds to specific nuclear matrix attachment regions of the DNA and regulates genes involved in a variety of important biological process, involving rapid growth, differentiation, apoptosis, DNA recovery, transcription, and expression profile reprogramming . Recently, SATB1 expression has been shown to correlate with unfavorable tumor characteristics in various types of cancer by promoting enhanced tumor growth and malignant metastasis . Limited data are available regarding the influence of SATB1 expression on ESCC growth and progression.…”

“…15 Recently, SATB1 expression has been shown to correlate with unfavorable tumor characteristics in various types of cancer by promoting enhanced tumor growth and malignant metastasis. [16][17][18] Limited data are available regarding the influence of SATB1 expression on ESCC growth and progression. To investigate the role of SATB1 in ESCC, we evaluated SATB1 expression in ESCC tissues by immunohistochemistry.…”