TY - JOUR
T1 - The extent of proliferative and apoptotic activity in intraductal and invasive ductal breast carcinomas detected by Ki-67 labeling and terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling
AU - Shen, Kuo Liang
AU - Harn, Horng Jyh
AU - Ho, Li Ing
AU - Yu, Cheng Ping
AU - Chiu, Shao Chih
AU - Lee, Wei Hwa
PY - 1998/6/15
Y1 - 1998/6/15
N2 - BACKGROUND. The balance among cell proliferation, cell differentiation, and cell death determines the cell number in a population as well as the size or even the stage of a tumor. Thus, to improve our understanding of the pathogenesis of neoplasms, it is important to investigate the regulation of both cell proliferation and cell death. METHODS. This study examined the occurrence of apoptosis and proliferative capacity in 46 breast carcinomas: 20 intraductal carcinomas (ductal carcinomas in situ [DCIS]) and 26 infiltrative ductal carcinomas (IDC). Terminal deoxynucleotidyl transferase- mediated digoxigenin-11-dUTP nick end labeling (TUNEL) and immunostaining with the Ki-67 antibody were used in the examination. A ladder of DNA fragments induced by apoptosis was demonstrated by means of DNA agarose gel electrophoresis in 10 of the available TUNEL positive and negative samples. RESULTS. The results were correlated with p53, bcl-2, estrogen receptor (ER), and progesterone receptor (PR) protein expression, which would suggest association with apoptosis by immunohistochemistry. The apoptosis and proliferation of each cancer were expressed as the number of tumor cells undergoing apoptosis and proliferation per 1000 tumor cells. The extent of apoptosis was more frequently observed in DCIS than in IDC (21.9 ± 6.8 vs. 4.0 ± 0.9, P < 0.001), and the proliferation activity was significantly higher in IDC than in DCIS (16.8 ± 6.5 vs. 3.5 ± 0.8, P < 0.006). Apoptosis associated with MIB-1 positive cells and TUNEL labeling was significantly higher in IDC than in DCIS (3.26 vs. 0.42, P = 0.001). In DCIS, apoptosis was correlated with p53 (r = 0.663, P = 0.005), and p53 had a reverse correlation with bcl-2 (r = 0.620, P = 0.018). Moreover, bcl-2 expression was associated with ER (P = 0.028) and PR (P = 0.005) expression in both DCIS and IDC. CONCLUSIONS. The results of this study show that a higher degree of apoptosis and lower proliferation activity in intraductal carcinoma result in a steady- state, self-renewing condition in which net growth of the tumor is rare. The results also indicate that apoptosis was altered by the expression of p53, bcl-2, ER, and PR.
AB - BACKGROUND. The balance among cell proliferation, cell differentiation, and cell death determines the cell number in a population as well as the size or even the stage of a tumor. Thus, to improve our understanding of the pathogenesis of neoplasms, it is important to investigate the regulation of both cell proliferation and cell death. METHODS. This study examined the occurrence of apoptosis and proliferative capacity in 46 breast carcinomas: 20 intraductal carcinomas (ductal carcinomas in situ [DCIS]) and 26 infiltrative ductal carcinomas (IDC). Terminal deoxynucleotidyl transferase- mediated digoxigenin-11-dUTP nick end labeling (TUNEL) and immunostaining with the Ki-67 antibody were used in the examination. A ladder of DNA fragments induced by apoptosis was demonstrated by means of DNA agarose gel electrophoresis in 10 of the available TUNEL positive and negative samples. RESULTS. The results were correlated with p53, bcl-2, estrogen receptor (ER), and progesterone receptor (PR) protein expression, which would suggest association with apoptosis by immunohistochemistry. The apoptosis and proliferation of each cancer were expressed as the number of tumor cells undergoing apoptosis and proliferation per 1000 tumor cells. The extent of apoptosis was more frequently observed in DCIS than in IDC (21.9 ± 6.8 vs. 4.0 ± 0.9, P < 0.001), and the proliferation activity was significantly higher in IDC than in DCIS (16.8 ± 6.5 vs. 3.5 ± 0.8, P < 0.006). Apoptosis associated with MIB-1 positive cells and TUNEL labeling was significantly higher in IDC than in DCIS (3.26 vs. 0.42, P = 0.001). In DCIS, apoptosis was correlated with p53 (r = 0.663, P = 0.005), and p53 had a reverse correlation with bcl-2 (r = 0.620, P = 0.018). Moreover, bcl-2 expression was associated with ER (P = 0.028) and PR (P = 0.005) expression in both DCIS and IDC. CONCLUSIONS. The results of this study show that a higher degree of apoptosis and lower proliferation activity in intraductal carcinoma result in a steady- state, self-renewing condition in which net growth of the tumor is rare. The results also indicate that apoptosis was altered by the expression of p53, bcl-2, ER, and PR.
KW - Apoptosis
KW - Bcl-2
KW - Breast carcinoma
KW - Estrogen receptor
KW - Infiltrative ductal carcinoma
KW - Intraductal carcinoma (ductal carcinoma in situ)
KW - MIB-1
KW - Progesterone receptor
KW - TUNEL
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=0032526164&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032526164&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0142(19980615)82:12<2373::AID-CNCR11>3.0.CO;2-M
DO - 10.1002/(SICI)1097-0142(19980615)82:12<2373::AID-CNCR11>3.0.CO;2-M
M3 - Article
C2 - 9635530
AN - SCOPUS:0032526164
SN - 0008-543X
VL - 82
SP - 2373
EP - 2381
JO - Cancer
JF - Cancer
IS - 12
ER -