Role of immunohistochemical identification of Her-2/neu and detection of variability in overexpression in pancreatic carcinoma.
BACKGROUND
Her-2/neu overexpression has been recently shown to be a poor prognostic factor in breast carcinoma. Overexpression has also been demonstrated in adenocarcinoma of the pancreas but the significance is unclear. We attempted to study the role of Her-2/neu overexpression, detected by immunohistochemistry, in pancreatic carcinoma and also examined for variability of overexpression across different tissue sections on individual tumor specimen.


METHODS
Records of all patients with adenocarcinoma of the pancreas, diagnosed and followed between 1986 and 2001 at a tertiary care oncology center were reviewed. Archival pathological samples were analyzed for Her-2/neu expression using the Hercep immunohistochemical assay (DAKO). A score of 2+ or greater on the assay was considered positive for Her-2/neu expression. When tumors were found to be Her-2/neu-positive, they were assessed for variability of expression of Her-2/neu by staining different sections of individual tumor blocks. Log-rank tests and Cox proportional hazards methods were used to analyze survival data.


RESULTS
Three hundred and eight patients were included in our study. The mean age was 70 years. Forty-eight out of 308 specimens (16%) were positive for Her-2/neu expression. The mean survival in the Her-2/neu-positive group was 11 months and in the Her-2/neu-negative group was 7 months (p=.03). Of the 48 patients with Her-2/neu-positive tumors, 16 showed variable overexpression (33%). Multivariate analysis did not reveal statistical difference in survival between the uniformly expressing and variably expressing tumors.


CONCLUSIONS
Her-2/neu overexpression detected by immunohistochemistry does not appear to be a poor prognostic factor in patients with adenocarcinoma of the pancreas. Also, there is significant variability in the level of Her-2/neu expression across tumor sections in individual patients, which can potentially lead to considerable misclassification. Hence, we believe that, pending further studies, Her-2/neu may not be an appropriate target for therapy in pancreatic adenocarcinoma.
Koka
Vijay
V
Department of Internal Medicine, University of North Dakota School of Medicine and Health Sciences, Fargo 58102, USA.
Potti
Anil
A
Koch
Michael
M
Fraiman
Genise
G
Mehdi
Syed
S
Levitt
Ralph
R
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate
D018719:Erb-b2 Receptor Tyrosine Kinases