title: Prognostic and treatment predictive significance of SATB1 and SATB2 expression in pancreatic and periampullary adenocarcinoma.
abstract: BACKGROUND
  Pancreatic 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.
  
  
  METHODS
  Immunohistochemical 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).
  
  
  RESULTS
  Positive 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. jacob.elebro@med.lu.se.
authors.forename: Jacob
authors.initials: J
authors.lastname: Elebro
authors.affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. margareta.heby@med.lu.se.
authors.forename: Margareta
authors.initials: M
authors.lastname: Heby
authors.affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. alexander.gaber@med.lu.se.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gaber
authors.affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. bjorn.nodin@med.lu.se.
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. liv.jonsson@med.lu.se.
authors.forename: Liv
authors.initials: L
authors.lastname: Jonsson
authors.affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. richard.fristedt@med.lu.se.
authors.forename: Richard
authors.initials: R
authors.lastname: Fristedt
authors.affiliation: Science for Life Laboratory, Royal Institute of Technology, 171 21, Stockholm, Sweden. mathias.uhlen@scilifelab.se.|School of Biotechnology, AlbaNova University Center, Royal Institute of Technology, 106 91, Stockholm, Sweden. mathias.uhlen@scilifelab.se.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. karin.jirstrom@med.lu.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. jakob.eberhard@med.lu.se.
authors.forename: Jakob
authors.initials: J
authors.lastname: Eberhard
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C076189:SATB1 protein, human; C521297:SATB2 protein, human; D014157:Transcription Factors