title: Differential Protein Expression in Small Intestinal Neuroendocrine Tumors and Liver Metastases.
abstract: OBJECTIVE
  Small intestinal neuroendocrine tumors (SI-NETs) are often detected after they have become metastatic. Using a novel protein array, we identified pathways important in SI-NET metastasis development in surgically resected patients.
  
  
  METHODS
  Paired primary tumors and liver metastases from 25 patients undergoing surgical resection for metastatic SI-NETs were harvested. Extracted proteins were separated by sodium dodecyl sulfate gel and multiplex immunoblots were performed with 136 antibodies. Significant Analysis of Microarray was used to select for differentially expressed proteins. A tissue microarray was constructed from 27 archived specimens and stained by immunohistochemistry.
  
  
  RESULTS
  Comparing primary SI-NETs with matched normal small-bowel mucosa, 9 proteins were upregulated and cyclin E was downregulated. The SI-NET liver metastases demonstrated upregulation of P-ERK and p27 but downregulation of CDK2 and CDC25B. When comparing primary SI-NET with their paired liver metastases, cyclin E demonstrated a significant upregulation in the liver metastasis. Tissue microarray demonstrated higher p38 expression and lower Cdc 25b expression in SI-NETs versus liver metastases and confirmed higher expression of p27 in liver metastases versus normal liver.
  
  
  CONCLUSIONS
  Few studies have compared protein expression in paired primary and metastatic SI-NETs. Our findings reveal changes in a limited number of proteins, suggesting that these may be targets for therapy.
authors.affiliation: From the Departments of *Medicine/Gastroenterology and †Pathology, Mount Sinai School of Medicine; ‡Liver Cancer Program, Hofstra-North Shore Long Island Jewish School of Medicine; §Department of Surgery/Division of Surgical Oncology, Mount Sinai School of Medicine; and ∥Mount Sinai Liver Cancer Program, Mount Sinai Hospital, New York, NY.
authors.forename: Michelle Kang
authors.initials: MK
authors.lastname: Kim
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Daguang
authors.initials: D
authors.lastname: Wang
authors.forename: Miao
authors.initials: M
authors.lastname: Cui
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Ward
authors.forename: Richard R P
authors.initials: RR
authors.lastname: Warner
authors.forename: Sasan
authors.initials: S
authors.lastname: Roayaie
authors.forename: Michail
authors.initials: M
authors.lastname: Shafir
authors.forename: Myron
authors.initials: M
authors.lastname: Schwartz
authors.forename: David
authors.initials: D
authors.lastname: Zhang
authors.forename: Steven
authors.initials: S
authors.lastname: Itzkowitz
mesh_terms: D056741:Cyclin D / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D046888:Tissue Array Analysis; D020687:cdc25 Phosphatases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D056741:Cyclin D; D020543:Proteome; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D048051:p38 Mitogen-Activated Protein Kinases; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases