Silencing of UCHL1 by CpG Promoter Hyper-methylation is Associated with Metastatic Gastroenteropancreatic Well-Differentiated Neuroendocrine (Carcinoid) Tumors

David A. Kleiman, Toni Beninato, Samuel Sultan, Michael J P Crowley, Brendan Finnerty, Ritu Kumar, Nicole C. Panarelli, Yi Fang Liu, Michael D. Lieberman, Marco Seandel, Todd Evans, Olivier Elemento, Rasa Zarnegar, Thomas J. Fahey

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors with varying metastatic potential. The underlying molecular basis for metastasis by GEP-NETs remains undefined.

Methods: Quantitative PCR and immunohistochemistry (IHC) staining for ubiquitin carboxyl-terminal esterase L1 (UCHL1) gene and protein expression was performed on a group of localized and metastatic well-differentiated GEP-NET samples acquired from a prospectively maintained tissue bank. The ability of extent of UCHL1 IHC staining to differentiate localized and metastatic tumors was compared with Ki-67 index.

Results: Among 46 total samples, UCHL1 expression at both the gene and protein level was significantly greater among localized GEP-NETs compared with metastatic tumors and metastases (p 

Conclusions: Loss of UCHL1 expression by CpG promoter hypermethylation is associated with metastatic GEP-NETs. Extent of UCHL1 staining should be explored as a potentially clinically useful adjunct to Ki-67 index in evaluating GEP-NETs for aggressive features.

Original languageEnglish (US)
Pages (from-to)672-679
Number of pages8
JournalAnnals of Surgical Oncology
Volume21
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Neuroendocrine Tumors
Carcinoid Tumor
Methylation
Staining and Labeling
Ubiquitin Thiolesterase
Immunohistochemistry
Tissue Banks
Neoplasm Metastasis
Neoplasms
Esterases
Ubiquitin
Gastro-enteropancreatic neuroendocrine tumor
Proteins
Gene Expression
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Silencing of UCHL1 by CpG Promoter Hyper-methylation is Associated with Metastatic Gastroenteropancreatic Well-Differentiated Neuroendocrine (Carcinoid) Tumors. / Kleiman, David A.; Beninato, Toni; Sultan, Samuel; Crowley, Michael J P; Finnerty, Brendan; Kumar, Ritu; Panarelli, Nicole C.; Liu, Yi Fang; Lieberman, Michael D.; Seandel, Marco; Evans, Todd; Elemento, Olivier; Zarnegar, Rasa; Fahey, Thomas J.

In: Annals of Surgical Oncology, Vol. 21, No. 4, 2014, p. 672-679.

Research output: Contribution to journalArticle

Kleiman, DA, Beninato, T, Sultan, S, Crowley, MJP, Finnerty, B, Kumar, R, Panarelli, NC, Liu, YF, Lieberman, MD, Seandel, M, Evans, T, Elemento, O, Zarnegar, R & Fahey, TJ 2014, 'Silencing of UCHL1 by CpG Promoter Hyper-methylation is Associated with Metastatic Gastroenteropancreatic Well-Differentiated Neuroendocrine (Carcinoid) Tumors', Annals of Surgical Oncology, vol. 21, no. 4, pp. 672-679. https://doi.org/10.1245/s10434-014-3787-2
Kleiman, David A. ; Beninato, Toni ; Sultan, Samuel ; Crowley, Michael J P ; Finnerty, Brendan ; Kumar, Ritu ; Panarelli, Nicole C. ; Liu, Yi Fang ; Lieberman, Michael D. ; Seandel, Marco ; Evans, Todd ; Elemento, Olivier ; Zarnegar, Rasa ; Fahey, Thomas J. / Silencing of UCHL1 by CpG Promoter Hyper-methylation is Associated with Metastatic Gastroenteropancreatic Well-Differentiated Neuroendocrine (Carcinoid) Tumors. In: Annals of Surgical Oncology. 2014 ; Vol. 21, No. 4. pp. 672-679.
@article{1504c342ca2c41dc8aa7227afc1ffff3,
title = "Silencing of UCHL1 by CpG Promoter Hyper-methylation is Associated with Metastatic Gastroenteropancreatic Well-Differentiated Neuroendocrine (Carcinoid) Tumors",
abstract = "Background: Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors with varying metastatic potential. The underlying molecular basis for metastasis by GEP-NETs remains undefined.Methods: Quantitative PCR and immunohistochemistry (IHC) staining for ubiquitin carboxyl-terminal esterase L1 (UCHL1) gene and protein expression was performed on a group of localized and metastatic well-differentiated GEP-NET samples acquired from a prospectively maintained tissue bank. The ability of extent of UCHL1 IHC staining to differentiate localized and metastatic tumors was compared with Ki-67 index.Results: Among 46 total samples, UCHL1 expression at both the gene and protein level was significantly greater among localized GEP-NETs compared with metastatic tumors and metastases (p Conclusions: Loss of UCHL1 expression by CpG promoter hypermethylation is associated with metastatic GEP-NETs. Extent of UCHL1 staining should be explored as a potentially clinically useful adjunct to Ki-67 index in evaluating GEP-NETs for aggressive features.",
author = "Kleiman, {David A.} and Toni Beninato and Samuel Sultan and Crowley, {Michael J P} and Brendan Finnerty and Ritu Kumar and Panarelli, {Nicole C.} and Liu, {Yi Fang} and Lieberman, {Michael D.} and Marco Seandel and Todd Evans and Olivier Elemento and Rasa Zarnegar and Fahey, {Thomas J.}",
year = "2014",
doi = "10.1245/s10434-014-3787-2",
language = "English (US)",
volume = "21",
pages = "672--679",
journal = "Annals of Surgical Oncology",
issn = "1068-9265",
publisher = "Springer New York",
number = "4",

}

TY - JOUR

T1 - Silencing of UCHL1 by CpG Promoter Hyper-methylation is Associated with Metastatic Gastroenteropancreatic Well-Differentiated Neuroendocrine (Carcinoid) Tumors

AU - Kleiman, David A.

AU - Beninato, Toni

AU - Sultan, Samuel

AU - Crowley, Michael J P

AU - Finnerty, Brendan

AU - Kumar, Ritu

AU - Panarelli, Nicole C.

AU - Liu, Yi Fang

AU - Lieberman, Michael D.

AU - Seandel, Marco

AU - Evans, Todd

AU - Elemento, Olivier

AU - Zarnegar, Rasa

AU - Fahey, Thomas J.

PY - 2014

Y1 - 2014

N2 - Background: Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors with varying metastatic potential. The underlying molecular basis for metastasis by GEP-NETs remains undefined.Methods: Quantitative PCR and immunohistochemistry (IHC) staining for ubiquitin carboxyl-terminal esterase L1 (UCHL1) gene and protein expression was performed on a group of localized and metastatic well-differentiated GEP-NET samples acquired from a prospectively maintained tissue bank. The ability of extent of UCHL1 IHC staining to differentiate localized and metastatic tumors was compared with Ki-67 index.Results: Among 46 total samples, UCHL1 expression at both the gene and protein level was significantly greater among localized GEP-NETs compared with metastatic tumors and metastases (p Conclusions: Loss of UCHL1 expression by CpG promoter hypermethylation is associated with metastatic GEP-NETs. Extent of UCHL1 staining should be explored as a potentially clinically useful adjunct to Ki-67 index in evaluating GEP-NETs for aggressive features.

AB - Background: Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors with varying metastatic potential. The underlying molecular basis for metastasis by GEP-NETs remains undefined.Methods: Quantitative PCR and immunohistochemistry (IHC) staining for ubiquitin carboxyl-terminal esterase L1 (UCHL1) gene and protein expression was performed on a group of localized and metastatic well-differentiated GEP-NET samples acquired from a prospectively maintained tissue bank. The ability of extent of UCHL1 IHC staining to differentiate localized and metastatic tumors was compared with Ki-67 index.Results: Among 46 total samples, UCHL1 expression at both the gene and protein level was significantly greater among localized GEP-NETs compared with metastatic tumors and metastases (p Conclusions: Loss of UCHL1 expression by CpG promoter hypermethylation is associated with metastatic GEP-NETs. Extent of UCHL1 staining should be explored as a potentially clinically useful adjunct to Ki-67 index in evaluating GEP-NETs for aggressive features.

UR - http://www.scopus.com/inward/record.url?scp=84939883075&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939883075&partnerID=8YFLogxK

U2 - 10.1245/s10434-014-3787-2

DO - 10.1245/s10434-014-3787-2

M3 - Article

C2 - 24854489

AN - SCOPUS:84939883075

VL - 21

SP - 672

EP - 679

JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

SN - 1068-9265

IS - 4

ER -