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.


CONCLUSIONS
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.
Zhao
Haiying
H
The University of Tokushima, 3-18-5 Kuramoto-cho, Tokushima 770-0052, Japan.
Morimoto
Tadaoki
T
Sasa
Mitsunori
M
Tanaka
Takashi
T
Izumi
Keisuke
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology*; D002402:Cathepsin D / Q000032:analysis / Q000378:metabolism*; D016009:Chi-Square Distribution; D046508:Culture Techniques; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000378:metabolism*; D011336:Probability; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012680:Sensitivity and Specificity; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000378:metabolism*
D014408:Biomarkers, Tumor; D002402:Cathepsin D; D019394:Ki-67 Antigen; D017395:Plasminogen Activator Inhibitor 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D014568:Urokinase-Type Plasminogen Activator