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Heterogeneous Expression of erbB-2 Messenger RNA in Human Breast Cancer

Rorer Biotech, Inc., King of Prussia, Pennsylvania 1900 [C. R. K., L. P.], and the National Cancer Institute, NIH [S. M. Sw., S. M. St., M. E. L., E. P. G.], Bethesda, Maryland 20892

Amplification and mRNA expression of the erbB-2 gene was analyzed in 61 samples of primary human breast carcinoma. In the 57 samples where RNA could be isolated four different expression level groups were identified. Comparison of hybridization signal with that for ß-actin revealed that erbB-2 mRNA could not be detected in 6 of 57 samples (11%), was detected at normal levels in 32 of 57 samples (56%), showed 4- to 8-fold overexpression in 8 of 57 samples (14%), and showed 16- to 128-fold overexpression in 11 of 57 samples (19%). Examination of the DNA of the same set of samples revealed 6 of 61 samples (10%) with distinct gene amplification and 6 of 61 samples (10%) with possible gene amplification. The highest levels of erbB-2 overexpression were associated with gene amplification. Samples with 4- to 16-fold overexpression of the erbB-2 mRNA occurred without evident gene abnormalities. There was no association of erbB-2 expression or gene amplification with clinical stage of breast carcinoma or axillary lymph node involvement. The clear amplification of the erbB-2 gene may be associated with a significantly shorter time to treatment failure.

¹ To whom requests for reprints should be addressed, at Molecular Oncology, Inc., 19 Firstfield Road, Gaithersburg, MD 20878.

Received 10/13/88. Revised 4/ 3/89. Accepted 4/26/89.

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