Histologic grade and p53 immunoreaction as indicators of early recurrence of node-negative breast cancer

Even among breast cancer patients without metastasis to axillary lymph nodes, early recurrence can occur. To determine the risk factors for early recurrence, we performed a case-control study between 32 patients with an early recurrence of breast cancer and 122 patients without recurrence, in which tumor size, age of patient and date of operation were matched. In all 154 node-negative patients, followed up over a 13.1-year median period, expression of p53, c-erbB-2 and cathepsin D in the primary tumor were studied immunohistochemically in paraffin-embedded tissues and were compared with morphologic factors such as histologic grade and invasive growth. Univariate analysis showed that nuclear p53 immunoreaction was significantly predictive of early recurrence [risk ratio (RR) 3.3]. Likewise, cathepsin D (RR 0.22) was significantly negatively associated; however, when the risk ratio was analyzed in terms of intensity of cathepsin D staining, no superior survival was found for patients with strongly positive tumors. Overexpression of c-erbB-2 protein was not associated with outcome by either univariate or multivariate analysis. As a whole, histologic grade was confirmed as being a strong predictor (RR 42.6) and multivariate analysis showed that only histologic grade was a significant risk factor for early recurrence. p53 immunoreaction was not a significant independent factor because it was closely linked to histologic grade (P = 0.002), especially to a high mitotic index (P < 0.001). Moreover, in 14 patients with "special histologic types' of invasive carcinomas and no recurrence, all were p53-negative except one medullary carcinoma. Nuclear p53 immunoreaction is useful in supporting histologic grade to detect a high-risk for early recurrence in node-negative patients who may be eligible for systemic adjuvant therapy.