The H-ras oncogene product p21 and prognosis in human breast cancer.

The protein product of the H-ras oncogene, p21, has been measured semiquantitatively in solubilized particulate fractions of 160 primary tumours from patients presenting without evidence of distant metastatic breast cancer. Levels of p21 have then been related to factors of established prognostic significance, and to clinical outcome after primary treatment in terms of disease-free interval and survival times. p21 was detected by Western blotting in all tumour fractions, but amounts varied markedly between different tumours. There was no significant relationship between levels of p21 and the menopausal status of the patient, tumour oestrogen receptors, grade, and clinical stage. However, there was a significant trend for tumours to be associated with lymph node involvement as p21 was increasingly expressed. Elevated levels of p21 were also significantly related to early disease recurrence and death from cancer. Multivariate stepwise analysis showed that both p21 and lymph node status were independent statistically significant factors for disease recurrence and survival, and that no other parameter was significant for clinical outcome after adjustment for p21 and lymph node status. These results indicate that tumour levels of p21 are an important prognostic variable in patients with early breast cancer.