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.

c-erbB-3 protein expression in human breast cancer: comparison with other tumour variables and survival.

c-erbB-3 protein expression was investigated immunohistochemically in a series of 97 malignant breast tumours using the monoclonal antibody RTJ1. Twenty-eight cases (28.8%) showed c-erbB-3 overexpression, 31 cases (32%) showed normal levels of c-erbB-3 and 38 cases (39.2%) were c-erbB-3 negative. c-erbB-3 overexpression was positively but not significantly related to negative lymph node status and survival over a 10-year follow-up period.

Experimental paracetamol-induced hepatic necrosis: a light- and electron-microscope, and histochemical study.

Rats were killed at various time-intervals up to 48 hr after a single large dose of paracetamol (3 g per kg) and their livers examined by light and electron microscopy. In general, this revealed glycogen depletion, loss of ribosomes, and cytoplasmic matrix swelling commencing 3-6 hr after administration which in centrilobular hepatocytes progressed to frank coagulative necrosis at 12-24 hr. Midzonal cells showed more prominent aqueous swelling with besiculation of the endoplasmic reticulum, and in some cells, gross hydropic vacuolation.