Apoptosis in human breast and gastrointestinal carcinomas. Detection in histological sections with monoclonal...

We report application of a novel immunohistochemical procedure for the staining of apoptotic (AP) cells in paraffin sections using monoclonal antibody (MAb) to single-stranded DNA. MAb differentiated between apoptosis and necrosis and in contrast to in situ end labelling specifically stained only AP cells. AP carcinoma cells stained with the antibody were detected in 32 of 58 infiltrating human breast carcinomas and in 9 of 15 colon adenocarcinomas. Stromal cells stained with the MAb were observed in all carcinomas, including those in which no AP carcinoma cells were detected. There was a strong positive correlation between the presence of AP cells, loss of hormone receptors and a high proliferation rate in breast carcinomas. AP cells were present in 80-87% of receptor-negative carcinomas, while most of receptor-positive breast carcinomas did not contain AP cells. Apoptosis in tumor cells was detected significantly more frequently among breast carcinomas with high, than among carcinomas with low S-phase fraction. AP cells were present in 93-95% of breast carcinomas which were receptor-negative and had a high S-phase fraction. Immunostaining demonstrated a strong positive correlation between the loss of bcl-2 protein and intensive apoptosis in breast carcinomas. Association between apoptosis and markers of poor prognosis in breast cancer (loss of hormone receptors, intensive proliferation, loss of bcl-2 protein) indicates that apoptotic cell death is typical of more aggressive carcinomas.