Overexpression of HER2/neu oncogene in human pancreatic carcinoma.
The HER2/neu oncogene encodes a transmembrane protein that possesses intrinsic tyrosine kinase activity. Its overexpression has been associated with the malignant phenotype. In this study we examined HER2/neu expression in the normal and cancerous human pancreas. In the normal pancreas HER2/neu immunostaining was observed in acinar and ductal cells. HER2/neu immunoreactivity was expressed in 34 of 76 (45%) pancreatic carcinomas. There was a significant correlation between tumors with well-differentiated histology and HER2/neu expression. Northern blot analysis demonstrated HER2/neu mRNA expression in the normal pancreas and in situ hybridization confirmed its distribution in both acinar and ductal cells. In cancer tissues Northern blot analysis indicated that HER2/neu mRNA levels were elevated in 13 of 25 (52%) of the tumors in comparison with the normal tissues. In addition, in situ hybridization demonstrated a strong but heterogenous distribution of mRNA grains in these tumors. Southern blot analysis did not demonstrate HER2/neu gene amplification in any of the tumors. These data indicate that the HER2/neu protein is synthesized in the normal exocrine pancreas and is frequently overexpressed in well-differentiated adenocarcinomas of the pancreas as a result of increased HER2/neu mRNA levels.
Yamanaka
Y
Y
Department of Medicine, University of California, Irvine 92717.
Friess
H
H
Kobrin
M S
MS
Büchler
M
M
Kunz
J
J
Beger
H G
HG
Korc
M
M
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000032:analysis*; D010179:Pancreas / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D012334:RNA, Neoplasm / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases
D009856:Oncogene Proteins, Viral; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases