Loss of bcl-2 expression in ductal carcinoma in situ of the breast relates to poor histological differentiation and to expression of p53 and c-erbB-2 proteins

Aim: This study (1) investigates the incidence of bcl-2 protein expression in a series of 108 cases of ductal carcinoma in situ (DCIS), including 25 with early invasive carcinoma, and (2) evaluates the relationship of bcl-2 expression to the histological grade of DCIS and to the expression of oestrogen receptor (ER), c-erbB-2 and p53 proteins. Methods and results: The expression of bcl-2, oestrogen receptor (ER), c-erbB-2 and p53 proteins was determined immunohistochemically. Cases were regarded as positive for individual antibodies when at least 10% of the DCIS cells showed positive staining. DCIS was graded histologically as well (n = 9), intermediately (n = 24), or poorly differentiated (n = 75). bcl-2 expression was documented in 57 cases (53%) and was strongly associated with the histological grade of DCIS (P < 0.0001). All cases of well-differentiated DCIS were bcl-2 positive and loss of bcl-2 expression was almost exclusively confined to poorly differentiated DCIS lesions. bcl-2 expression was also closely associated with positive ER status (P < 0.0001). Forty-seven of 57 (82%) bcl-2 positive cases were ER positive while 49/51 (96%) bcl-2 negative cases were ER negative. There was a significant inverse correlation between bcl-2 expression and both p53 protein expression (P = 0.0004) and c-erbB-2 expression (P < 0.0001). Nineteen of 24 (79%) p53 positive cases and 38/45 (84%) c-erbB-2 positive cases showed loss of bcl-2, Conclusions: Loss of bcl-2 expression occurs in poorly differentiated DCIS and is related to negative ER status and to positive p53 and c-erbB-2 status. This pattern of bcl-2 expression and its association with other biological markers in DCIS is similar to that reported in invasive breast carcinoma.