P53 AND C-ERBB-2 ALTERATIONS IN IN-SITU AND INVASIVE DUCTAL BREAST CARCINOMAS - A GENETIC AND IMMUNOHISTOCHEMICAL ANALYSIS

p53 mutations, c-erbB-2 amplifications and expression of the related p roteins were evaluated in a panel of ductal breast carcinomas selected on the basis of their invasive component. The tumors comprised: 8 duc tal carcinomas in situ (DCIS); 8 carcinomas with a minimal (less than 20%) invasive component, hereafter referred to as DCIC (<20%); 13 carc inomas with 20%-50% invasiveness, DCIC (20-50%), and 48 infiltrating c arcinomas with more than 50% invasive component, DCIC (>50%). Tumors w ere further subdivided into large pleomorphic cell type or small regul ar cell type. A strong association was present between p53 gene mutati ons and p53 protein overexpression (p<0.001) as well as between amplif ication of the c-erbB-2 gene and expression of its protein product (p= 0.006). p53 aberrations (gene mutation and/or protein overexpression) were observed in 1 (12%) of 8 DCIS, 1 (11%) of 9 DCIC (<20%), 3 (23%) of 13 DCIC (20%-50%), and 13 (28%) of 47 DCIC (>50%). Amplification an d/or overexpression of c-erbB-2 were found in 30 (39%) of the 77 breas t carcinomas analyzed and were more frequent in DCIC (<20%) and in DCI C (20%-50%) (56% and 46% respectively) than in DCIS or DCIC (>50%) (12 % and 38% respectively). Irrespective of the presence of invasion, tum ors with p53 or c-erbB-2 alterations showed more frequently large cell s with pleomorphic nuclei, (for p53, p=0.027; for c-erbB-2, p=0.014). Our data suggest that p53 and c-erbB-2 alerations may occur in the ear liest recognized phase of breast cancer and may be important in the ev olution of small cell to large cell mammary carcinoma during tumor pro gression.