title: Prognostic significance of MTOR pathway component expression in neuroendocrine tumors.
abstract: OBJECTIVE
  Clinical studies have implicated the mechanistic target of rapamycin (serine/threonine kinase; MTOR) pathway in the regulation of neuroendocrine tumor (NET) growth. We explored whether expression of MTOR pathway components has prognostic significance in NET patients.
  
  
  METHODS
  We evaluated immunohistochemical expression of MTOR and phospho (p) -MTOR; its downstream targets RPS6KB1, RPS6, and EIF4EBP1; and its upstream regulators, in a cohort of 195 archival neuroendocrine tumors. We correlated expression levels with clinical outcomes, after adjusting for other prognostic variables.
  
  
  RESULTS
  We observed anticipated correlations between expression of upstream components of the MTOR pathway and their downstream targets. Expression of PIK3CA, MTOR, or p-EIF4EBP1 was associated with high MKI67 (Ki-67) labeling index. We failed to identify clinical correlations associated with expression of the upstream regulators TSC1, TSC2, AKT, p-AKT, PDPK1, PTEN, PIK3R1, or PIK3CA. In contrast, high expression of MTOR or its activated downstream targets p-RPS6KB1, p-RPS6, or p-EIF4EBP1 was associated with adverse clinical outcomes.
  
  
  CONCLUSIONS
  Our observations suggest that expression of MTOR or its downstream targets may be adverse prognostic factors in neuroendocrine tumors.
authors: Zhi Rong Qian, Monica Ter-Minassian, Jennifer A. Chan, Yu Imamura, Susanne M. Hooshmand, Aya Kuchiba, Teppei Morikawa, Lauren K. Brais, Anastassia Daskalova, Rachel Heafield, Charles S. Fuchs, Shuji Ogino, Matthew H. Kulke, Dana-Farber Cancer Institute and Harvard Medical School; Monica Ter-Minassian, Xihong Lin, David C. Christiani, Shuji Ogino, Harvard School of Public Health; David C. Christiani, Massachusetts General Hospital, Harvard Medical School; Charles S. Fuchs, Shuji Ogino, Brigham and Women's Hospital, Boston, MA.
authors: Zhi Rong
authors: ZR
authors: Qian
authors: Monica
authors: M
authors: Ter-Minassian
authors: Jennifer A
authors: JA
authors: Chan
authors: Yu
authors: Y
authors: Imamura
authors: Susanne M
authors: SM
authors: Hooshmand
authors: Aya
authors: A
authors: Kuchiba
authors: Teppei
authors: T
authors: Morikawa
authors: Lauren K
authors: LK
authors: Brais
authors: Anastassia
authors: A
authors: Daskalova
authors: Rachel
authors: R
authors: Heafield
authors: Xihong
authors: X
authors: Lin
authors: David C
authors: DC
authors: Christiani
authors: Charles S
authors: CS
authors: Fuchs
authors: Shuji
authors: S
authors: Ogino
authors: Matthew H
authors: MH
authors: Kulke
mesh_terms: D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
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