PMID- 25482929
OWN - NLM
STAT- MEDLINE
DCOM- 20151130
LR  - 20201113
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 16
IP  - 2
DP  - 2015
TI  - PTCH 1 staining of pancreatic neuroendocrine tumor (PNET) samples from patients 
      with and without multiple endocrine neoplasia (MEN-1) syndrome reveals a 
      potential therapeutic target.
PG  - 219-24
LID - 10.4161/15384047.2014.987574 [doi]
AB  - Pancreatic neuroendocrine tumors (PNETs) are rare, indolent tumors that may occur 
      sporadically or develop in association with well-recognized hereditary syndromes, 
      particularly multiple endocrine neoplasia type 1 (MEN-1). We previously 
      demonstrated that the hedgehog (HH) signaling pathway was aberrantly up-regulated 
      in a mouse model that phenocopies the human MEN-1 syndrome, Men1l/l;RipCre, and 
      that inhibition of this pathway suppresses MEN-1 tumor cell proliferation. We 
      hypothesized that the HH signaling pathway is similarly upregulated in human 
      PNETs. We performed immunohistochemical (IHC) staining for PTCH1 in human fresh 
      and archival PNET specimens to examine whether human sporadic and 
      MEN-1-associated PNETs revealed similar abnormalities as in our mouse model and 
      correlated the results with clinical and demographic factors of the study cohort. 
      PTCH1 staining was positive in 12 of 22 PNET patients (55%). Four of 5 MEN-1 
      patients stained for PTCH1 (p = 0.32 as compared with sporadic disease patients). 
      Nine of 16 patients with metastatic disease stained for PTCH1 as compared with 
      zero of 3 with localized disease only (p = 0.21). No demographic or clinical 
      features appeared to be predictive of PTCH 1 positivity and PTCH 1 positivity per 
      se was not predictive of clinical outcome. PTCH1, a marker of HH pathway up 
      regulation, is detectable in both primary and metastatic tumors in more than 50% 
      of PNET patients. Although no clinical or demographic factors predict PTCH1 
      positivity and PTCH1 positivity does not predict clinical outcome, the frequency 
      of expression alone indicates that perturbation of this pathway with agents such 
      as Vismodegib, an inhibitor of Smoothened (SMO), should be examined in future 
      clinical trials.
FAU - Gurung, Buddha
AU  - Gurung B
AD  - a Abramson Family Cancer Research Center; Department of Cancer Biology ; 
      University of Pennsylvania School of Medicine ; Philadelphia , PA USA.
FAU - Hua, Xianxin
AU  - Hua X
FAU - Runske, Melissa
AU  - Runske M
FAU - Bennett, Bonita
AU  - Bennett B
FAU - LiVolsi, Virginia
AU  - LiVolsi V
FAU - Roses, Robert
AU  - Roses R
FAU - Fraker, Douglas A
AU  - Fraker DA
FAU - Metz, David C
AU  - Metz DC
LA  - eng
GR  - R01 CA178856/CA/NCI NIH HHS/United States
GR  - 1-RO1-CA-178856-01/CA/NCI NIH HHS/United States
GR  - UO1 CA 44974/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - 0 (PTCH1 protein, human)
RN  - 0 (Patched Receptors)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Ptch1 protein, mouse)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Adult
MH  - Cohort Studies
MH  - Combined Modality Therapy
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia/diagnosis/*metabolism/therapy
MH  - Neoplasm Grading
MH  - Neoplasm Metastasis
MH  - Neuroendocrine Tumors/diagnosis/*metabolism/therapy
MH  - Pancreatic Neoplasms/diagnosis/*metabolism/therapy
MH  - Patched Receptors
MH  - Patched-1 Receptor
MH  - Receptors, Cell Surface/*metabolism
MH  - Treatment Outcome
MH  - Tumor Burden
PMC - PMC4623013
OTO - NOTNLM
OT  - ACTH, Adrenocorticotrophic hormone
OT  - BCNS, basal cell nevus syndrome
OT  - CgA, chromogranin A
OT  - HH, hedgehog
OT  - IHC, immunohistochemical
OT  - MEN-1
OT  - MEN-1, multiple neuroendocrine tumor syndrome type 1
OT  - NF-1, neurofibromatosis type 1
OT  - PNET, pancreatic neuroendocrine tumor
OT  - PRRT, peptide radioreceptor therapy
OT  - PTCH 1, protein patched homolog 1
OT  - SMO, smoothened
OT  - VHL, von Hippel Lan- dau
OT  - WHO, World Health Organization
OT  - hedgehog
OT  - neuroendocrine
OT  - pancreas
EDAT- 2014/12/09 06:00
MHDA- 2015/12/15 06:00
PMCR- 2015/11/21
CRDT- 2014/12/09 06:00
PHST- 2014/12/09 06:00 [entrez]
PHST- 2014/12/09 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2015/11/21 00:00 [pmc-release]
AID - 987574 [pii]
AID - 10.4161/15384047.2014.987574 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2015;16(2):219-24. doi: 10.4161/15384047.2014.987574.