Genetic mutations and expression of p53 in non-invasive breast lesions.

Breast carcinogenesis results from the accumulation of numerous somatic genetic alterations. Although mutations of the tumor suppressor gene p53 are among the most common alterations identified in invasive breast carcinomas, it is not clear whether its alteration occurs frequently in non-invasive breast lesions, including usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). p53 mutations were examined in 140 cases of non-invasive breast lesions, including UDH, ADH and DCIS, by high-resolution melting (HRM), followed by DNA sequence analysis. Two hundred and forty cases of non-invasive breast lesions were subjected to the immunohistochemical staining of p53 protein. The HRM and sequencing analysis demonstrated that the positive rates of p53 mutation were 0.0, 12.7 and 21.6% in UDH, ADH and DCIS, respectively. p53 protein expression was detected in none of the UDH, 14.6% of the ADH and 31.4% of the DCIS samples. Statistically, p53 mutation and protein accumulation gradually increased from UDH to ADH and to DCIS (P<0.05). There was a significantly positive association between p53 mutations and expression in these samples. p53 mutations and accumulation occur in non-invasive breast lesions, including ADH and DCIS, and may represent early events in breast carcinogenesis.