PMID- 16096400
OWN - NLM
STAT- MEDLINE
DCOM- 20051101
LR  - 20190823
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 29
IP  - 9
DP  - 2005 Sep
TI  - Assessment of HER-2 status in pancreatic adenocarcinoma: correlation of 
      immunohistochemistry, quantitative real-time RT-PCR, and FISH with aneuploidy and 
      survival.
PG  - 1125-34
AB  - HER-2 is a transmembrane growth factor receptor recognized in overexpression as 
      an independent adverse prognostic factor in several cancers. This study measured 
      HER-2 overexpression in pancreatic adenocarcinoma at the genetic, 
      transcriptional, and translational level. Expression was gauged with regard to 
      stage, grade, and survival. Pancreatic adenocarcinoma samples (n = 30) were 
      analyzed with immunohistochemical labeling for HER-2 protein, Quantitative 
      real-time reverse transcriptase polymerase chain reaction (Q-RT-PCR) measurement 
      of HER-2 mRNA and fluorescence in situ hybridization (FISH) analysis of HER-2 
      gene expression. HER-2 expression in benign pancreatic lesions (n = 10) provided 
      a control. Five (17%) of the pancreatic adenocarcinomas scored maximal 3+ 
      immunohistochemistry (IHC) labeling, seven (23%) had significantly increased 
      expression of HER-2 mRNA, while only one (3%) exhibited low level HER-2 gene 
      amplification. Ten (33%) tumors demonstrated aneuploidy. In general, concordance 
      between methodologies was poor, but the best agreement was seen between FISH 
      aneuploidy status and Q-RT-PCR mRNA overexpression (80% agreement), followed by 
      IHC and Q-RT-PCR (73% agreement). The least agreement was seen between IHC and 
      FISH aneuploidy status (67% agreement). Tumor stage was positively associated 
      with HER-2 mRNA and protein expression, but tumor grade and other patient 
      characteristics did not reach statistical significance. A poor survival outcome 
      was demonstrated with positive HER-2 status in all three measures of 
      overexpression (Kaplan-Meier log-rank score; P < 0.01 [IHC], P = 0.05 [Q-RT-PCR], 
      P = 0.02 [FISH]). Discordance in expression at the nuclear, cytoplasmic, and cell 
      surface levels highlights the limitations of immunohistochemical evaluation alone 
      and stresses the need for further evaluation of response to anti-HER-2 targeted 
      therapies in tumors displaying overexpression in gene copy, mRNA, and receptor 
      protein.
FAU - Saxby, Alex J
AU  - Saxby AJ
AD  - University of Sydney, Department of Surgery, Royal North Shore Hospital, 
      Australia.
FAU - Nielsen, Aiqun
AU  - Nielsen A
FAU - Scarlett, Christopher J
AU  - Scarlett CJ
FAU - Clarkson, Adele
AU  - Clarkson A
FAU - Morey, Adrienne
AU  - Morey A
FAU - Gill, Anthony
AU  - Gill A
FAU - Smith, Ross C
AU  - Smith RC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adenocarcinoma/*metabolism/mortality/*pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aneuploidy
MH  - Biomarkers, Tumor/analysis
MH  - Female
MH  - Gene Amplification
MH  - Gene Dosage
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Pancreatic Neoplasms/*metabolism/mortality/*pathology
MH  - Prognosis
MH  - RNA, Messenger/analysis
MH  - Receptor, ErbB-2/*metabolism
MH  - Reproducibility of Results
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survival Analysis
MH  - Survival Rate
EDAT- 2005/08/13 09:00
MHDA- 2005/11/03 09:00
CRDT- 2005/08/13 09:00
PHST- 2005/08/13 09:00 [pubmed]
PHST- 2005/11/03 09:00 [medline]
PHST- 2005/08/13 09:00 [entrez]
AID - 00000478-200509000-00001 [pii]
AID - 10.1097/01.pas.0000160979.85457.73 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2005 Sep;29(9):1125-34. doi: 
      10.1097/01.pas.0000160979.85457.73.