Immunohistochemical expression of uPA, PAI-1, cathepsin D and apoptotic cells in ductal carcinoma in situ of the breast.

BACKGROUND: We examined the relationship between biological markers, apoptotic indices and pathologic subtypes of ductal carcinoma in situ (DCIS) of the breast. The tumor-biological factors can be divided into invasive and proliferative markers. We chose urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and Cathepsin D as invasive markers, and Ki-67 and C-erbB2 oncoproteins as proliferative factors for our study.

METHODS: We used immunohistochemical methods to investigate the expression of uPA, PAI-1, Cathepsin D, Ki-67, C-erbB2 and ssDNA (single-stranded DNA for apoptotic cells) in 20 cases of DCIS. Tumor histological grade and the immunohistochemical expression of invasive and proliferative markers were compared.

RESULTS: Histological grade is associated with C-erbB2, MIB-1, apoptotic index (AI) and expression of PAI-1 in cancer and stroma. The correlation coefficient of the MIB-1 index and AI was 0.867. Of these invasive markers, only expression of PAI-1 in tumor and in stroma was associated with C-erbB2.

CONCLUSION: Our results show that the apoptosis index is closely related to the MIB-1 index, and also suggest that the immunohistochemical detection of PAI-1 in the cytoplasm of both carcinoma cells and stromal cells of DCIS is related to histological grade and expression of the proliferative markers MIB-1 and C-erbB2. Therefore, we infer that both invasiveness and proliferation are affected by the tumorigenesis of DCIS.