PMID- 11950922
OWN - NLM
STAT- MEDLINE
DCOM- 20020515
LR  - 20210103
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 15
IP  - 4
DP  - 2002 Apr
TI  - c-MYC activation in primary and metastatic ductal adenocarcinoma of the pancreas: 
      incidence, mechanisms, and clinical significance.
PG  - 462-9
AB  - Amplification and overexpression of c-MYC is a common event in various 
      neoplasias. Recently, comparative genomic hybridization (CGH) of primary 
      pancreatic adenocarcinomas revealed a distinct high-level amplification of 
      8q23-qter, suggesting that c-MYC located on 8q24 may be a candidate oncogene. To 
      evaluate the biological significance and prognostic value of c-MYC activation in 
      pancreatic carcinoma, we performed interphase fluorescence in situ hybridization 
      (FISH) and immunohistochemistry on a series of 69 primary pancreatic 
      adenocarcinomas, 19 corresponding lymph node metastases, and 5 pancreatic 
      intraductal lesions. Dual color FISH using a probe for c-MYC (8q24) and a 
      centromeric probe for chromosome 8 revealed amplification of c-MYC in 32.3% and 
      29.4% of primary and metastatic tumors, respectively. Immunostaining identified 
      c-MYC protein overexpression in 43.5% of primaries and 31.6% of metastases. Low 
      concordance between positive FISH and immunostaining (13.4%) suggests multiple 
      independent regulatory pathways of c-MYC activation. Statistical evaluation 
      revealed significant correlation (alpha = 0.033) between c-MYC protein 
      overexpression and histopathological tumor grade but absence of correlation with 
      tumor stage or lymph node status. Analysis of pancreatic intraductal lesions 
      showed c-MYC amplification and protein overexpression in two of five cases in 
      which invasive carcinoma exhibited identical aberrations. We conclude that 
      deregulation of c-MYC protein is common in pancreatic cancer and that it may be 
      involved in early neoplastic development and progression rather than in 
      locoregional spread of invasive cancer.
FAU - Schleger, C
AU  - Schleger C
AD  - Institute of Pathology, Universitatsklinikum Mannheim, Germany. 
      christiane.schleger@path.ma.uni-heidelberg.de
FAU - Verbeke, C
AU  - Verbeke C
FAU - Hildenbrand, R
AU  - Hildenbrand R
FAU - Zentgraf, H
AU  - Zentgraf H
FAU - Bleyl, U
AU  - Bleyl U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Proto-Oncogene Proteins c-myc)
SB  - IM
MH  - Adenocarcinoma/genetics/metabolism/*pathology
MH  - Carcinoma, Pancreatic Ductal/genetics/metabolism/*pathology
MH  - Data Interpretation, Statistical
MH  - Gene Amplification
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Neoplasm Metastasis
MH  - Pancreatic Neoplasms/genetics/metabolism/*pathology
MH  - Proto-Oncogene Proteins c-myc/biosynthesis/*genetics
EDAT- 2002/04/16 10:00
MHDA- 2002/05/16 10:01
CRDT- 2002/04/16 10:00
PHST- 2002/04/16 10:00 [pubmed]
PHST- 2002/05/16 10:01 [medline]
PHST- 2002/04/16 10:00 [entrez]
AID - 10.1038/modpathol.3880547 [doi]
PST - ppublish
SO  - Mod Pathol. 2002 Apr;15(4):462-9. doi: 10.1038/modpathol.3880547.