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Prognostic Significance of the Expression of a ras Protein with a Molecular Weight of 21,000 by Human Breast Cancer

Cellular Biochemistry Section [T. C., Y. S. C-C.], Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, and University Department of Clinical Surgery [W. R. M.], Royal Infirmary, Edinburgh, EH3 9YW, Scotland

Expression of the cellular ras M_r 21,000 protein (p21) has been measured in tumors from breast cancer patients who at time of presentation had no evidence of metastatic disease. Western blotting analysis revealed that 37 of 54 (69%) tumors contained p21 levels 2- to 10-fold greater than those of control breast tissues. An excessive increase of p21 (5- to 10-fold over the control value) occurred more frequently in tumors of T₃ and T₄ stages [15 of 25 (60%)] than in tumors at T₂ stage [6 of 29 (21%)], suggesting a correlation between advancement of disease and high p21 levels. p21 levels were positively related to the involvement of axillary lymph nodes at the time of primary treatment. As no correlations were detected between p21 levels and a gross pathological parameter, tumor grade, it is possible that p21 levels may reflect the degree of cellular malignancy. This is supported by data on tumor recurrence; 13 of 16 patients (81%) with tumors expressing low p21 levels were disease free for 4 years after primary treatment, whereas only 5 of 9 patients (56%) with high p21 tumors remained disease free. These results suggested that a quantitative enhancement of p21 oncogene protein is associated with both the progression and prognosis of breast cancer.

¹ To whom requests for reprints should be addressed, at the Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Building 10, Room 5B38, Bethesda, MD 20892.

Received 4/ 7/86. Revised 10/15/86. Revised 6/ 8/87. Accepted 7/23/87.

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