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Correlation of c-erbB-2 Gene Amplification and Protein Expression in Human Breast Carcinoma with Nodal Status and Nuclear Grading

Ludwig Institute for Cancer Research, Inselspital, 3010 Bern, Switzerland [S. S., B. G., N. E. H.]; Ludwig Institute for Cancer Research, Middlesex Hospital/University College Branch, 91 Riding House Street, London W1P 8BT, England [M. S. B., M. D. W.]; University Women's Hospital, Schanzeneckstrasse 1, 3012 Bern, Switzerland [G. W. L.]; and Institute of Cancer Research, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, England [W. J. G.]

Fifty-one primary human breast tumors were analyzed for amplification of the c-erbB-2 protooncogene. Thirteen (25%) of the DNA samples contained multiple gene copies. Paraffin-embedded tumor sections, available from 47 of the cases, were stained with a c-erbB-2 specific antiserum. Eighty-three % (10 of 12) of the tumors containing amplified c-erbB-2 gene copies stained positively with the c-erbB-2 specific antiserum (P = 0.03). Thirteen tumors containing single copy c-erbB-2 sequences also stained positively with the antiserum. This suggests that mechanisms other than gene amplification may lead to elevated levels of c-erbB-2 protein. Finally, there was a statistically significant correlation between c-erbB-2 protein expression and parameters used in breast cancer prognosis. Positive staining was associated with positive nodal status of the patient (P = 0.02) and with tumors showing a poor nuclear grade (P = 0.02). This is the first study showing that a determination of the level of c-erbB-2 protein in paraffin-embedded tumor sections may have prognostic value for the course of human breast cancer.

¹ Recipient of a Physician's Research Training Fellowship from the American Cancer Society. Present address: Hematology-Oncology Section, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104.

² To whom requests for reprints should be addressed.

Received 8/ 5/87. Revised 11/18/87. Accepted 12/ 4/87.

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