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1900
Evaluation of HER2/neu Expression in Lung Tumors
by Immunohistochemistry and Fluorescence in Situ Hybridization
(FISH). Fred Hirsch, Robert Veve, Mariliela Varella-Garcia,
Paul A Bunn, Wilbur A Franklin, Univ of Colorado HSC, Denver,
CO.
Herceptin, a humanized monoclonal antibody to the HER2/neu
oncoprotein, was originally developed as a treatment for breast
carcinoma but is now being evaluated in the treatment of lung
carcinoma. We have compared results of the Herceptest (Dako Corp.)
performed on paraffin sections to an alkaline
phosphatase-antialkaline phosphatase (APAAP) immunohistochemical
test on frozen sections using the monoclonal antibody 4D5 (a gift
from Brian Fendly, Genentech Corp.) in 36 lung carcinoma tumors
including 14 adenocarcinomas, 17 squamous carcinomas, 3 large cell
lung carcinomas (LCLC) and 2 small cell lung carcinomas (SCLC). Two
tumors strongly positive in both immunohistochemical procedures were
also tested by two-color FISH to evaluate levels of gene
amplification. Adenocarcinomas and LCLCs were more frequently
strongly positive than squamous tumors in the Herceptest (65% vs
29%) but not in the APAAP test (65% vs 82%). Low-level amplification
(1.3 and 1.5) of HER2/neu was detected in the two tumors tested by
FISH. We conclude that the results of immunohistochemical staining
for HER2/neu oncoprotein are methodologically dependent but that
adenocarcinoma and LCLC consistently express high levels of HER2/neu
oncoprotein regardless of testing method. Levels of gene
amplification in HER2/neu oncoprotein positive lung tumors may be
lower than levels in breast.
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