BACKGROUND The role of the anaphase-promoting complex (APC) is to promote the degradation of mitotic cyclins and other substrates involved in sister chromatid adhesions. The APC appears to be responsible for the degradation of cyclin B and may have a potential role in the loss of control concerning cell proliferation in mammalian cells. However, a direct link between the defects in the APC components and oncogenesis has not been estabilished. This study investigates the relationship between APC expression and variable prognostic factors in invasive ductal carcinoma of the breast. METHODS We evaluated 108 cases of invasive ductal carcinoma surgically resected from January, 1996 to May, 2000 at Wonju Christian Hospital, Wonju College of Medicine, Yonsei University. Immunohistochemical stains for APC, estrogen receptor, and Ki-67 were done in paraffin sections using the avidin-biotin complex method. The results were compared with clinical and pathologic parameters and flow cytometric DNA analysis factors. RESULTS Forty cases (37.0%) showed immunopositive reactions for APC. The APC positivity in histologic grades 1, 2, and 3 were 28 cases (84.4%), 33 cases (60.0%), and 7 cases (35.0%), respectively (p=0.0011). The APC expressions in cases with the number of mitosis of less than 10, 10-19, and more than 20 per 10 high power fields, were noted in 37 cases (75.5%), 26 cases (63.4%), and 5 cases (27.8%), respectively (p=0.0016). The mean value of the Ki-67 labeling index was 221.7 in the APC-positive group and 317.9 in the APC-negative group (p= 0.0091). DNA flow cytometric analysis revealed higher APC expressions in cases with diploid patterns (p=0.0095). The APC expression rate increased significantly with decreasing histologic grade, with decreasing mitotic activity, in cases with a low Ki-67 labeling index, and those in the diploid group (p<0.05). The APC expression was not statistically correlated with clinical stage, tumor size, and estrogen receptor status. CONCLUSIONS These findings suggest that positive APC expression may be considered as a good prognostic factor of invasive ductal carcinoma, and loss of APC expression may be related with the progression of breast cancer.
BACKGROUND Oncogene expression in Paget's disease of the breast is not well known. To characterize invasive ductal carcinoma associated with Paget's disease, we studied expression of anaphase promoting complex (APC) with its regulatory proteins. METHODS Immunohistochemical stainings were done with 10 cases of invasive ductal carcinoma associated with Paget's disease for APC, pituitary tumor transforming gene (PTTG), cyclin B1, p53, cyclin D1, and c-erbB-2. The expressions of these markers in Paget's disease were compared with those in the associated with carcinoma. RESULTS APC, PTTG, cyclin B1, and c-erbB-2 were positive in all of the cases with both Paget's disease and underlying carcinoma. p53 was expressed in Paget's disease of 6 cases (60%) and in carcinoma of 7 cases (70%). Cyclin D1 was positive in Paget's disease of 8 cases (80%) and in carcinoma of 9 cases (90%). CONCLUSIONS Breast carcinomas with Paget's disease seem to be distinguished by the high expression of APC, cyclin B1, PTTG, c-erbB2, and cyclin D1 in contrast to breast cancers without Paget's disease. Furthermore, the similar expression patterns of APC and APC regulatory proteins in both Paget's disease and underlying breast cancer support the epidermotropic theory as its pathogenetic mechanism.