title: RUNX1T1: a novel predictor of liver metastasis in primary pancreatic endocrine neoplasms.
abstract: OBJECTIVE
  Using gene expression profiling on frozen primary pancreatic endocrine tumors (PETs), we discovered RUNX1T1 as a leading candidate progression gene. This study was designed (1) to validate the differential expression of RUNX1T1 protein on independent test sets of metastatic and nonmetastatic PETs and (2) to determine if RUNX1T1 underexpression in primary tumors was predictive of liver metastases.
  
  
  METHODS
  Immunohistochemical expression of RUNX1T1 protein was quantified using Allred scores on archival metastatic (n = 13) and nonmetastatic (n = 24) primary adult PET tissues using custom-designed tissue microarrays. Wilcoxon rank sum/Fisher exact tests and receiver operating characteristic curves were used in the data analysis.
  
  
  RESULTS
  Median RUNX1T1 scores were 2 (2-7) and 6 (3-8) in metastatic versus nonmetastatic primaries (P < 0.0001). Eleven of 13 metastatic and 1 of 24 nonmetastatic primaries exhibited RUNX1T1-scores of 4 or less (P < 0.0001). Low RUNX1T1 expression was highly associated with hepatic metastases (P < 0.0001), whereas conventional histological criteria (Ki-67 index, mitotic rate, necrosis) were weakly associated with metastases (P = 0.08-0.15). Considering RUNX1T1 expression (Allred) score of 4 or less to be predictive, the sensitivity to predict hepatic metastases was 85%, with a specificity of 96%.
  
  
  CONCLUSIONS
  RUNX1T1 protein is underexpressed in well-differentiated metastatic primary PETs relative to nonmetastatic primaries and emerges as a promising novel biomarker for prediction of liver metastases.
authors.affiliation: Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. nasir_aejaz@lilly.com
authors.forename: Aejaz
authors.initials: A
authors.lastname: Nasir
authors.forename: James
authors.initials: J
authors.lastname: Helm
authors.forename: Leslie
authors.initials: L
authors.lastname: Turner
authors.forename: Dung-Tsa
authors.initials: DT
authors.lastname: Chen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Strosberg
authors.forename: Naiel
authors.initials: N
authors.lastname: Hafez
authors.forename: Evita B
authors.initials: EB
authors.lastname: Henderson-Jackson
authors.forename: Pamela
authors.initials: P
authors.lastname: Hodul
authors.forename: Marilyn M
authors.initials: MM
authors.lastname: Bui
authors.forename: Nelly A
authors.initials: NA
authors.lastname: Nasir
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Hakam
authors.forename: Mokenge P
authors.initials: MP
authors.lastname: Malafa
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Yeatman
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.forename: Larry K
authors.initials: LK
authors.lastname: Kvols
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000075142:RUNX1 Translocation Partner 1 Protein; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D014157:Transcription Factors