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

Kuo Liang Shen, Horng Jyh Harn, Li Ing Ho, Cheng Ping Yu, Shao Chih Chiu, Wei Hwa Lee

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2373-2381
Number of pages9
JournalCancer
Volume82
Issue number12
DOIs
Publication statusPublished - Jun 15 1998
Externally publishedYes

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Carcinoma, Ductal, Breast
DNA Nucleotidylexotransferase
Carcinoma, Intraductal, Noninfiltrating
Apoptosis
Ductal Carcinoma
In Situ Nick-End Labeling
Progesterone Receptors
Estrogen Receptors
Neoplasms
Cell Death
Cell Count
Cell Proliferation
digoxigenin-11-deoxyuridine triphosphate
Agar Gel Electrophoresis
DNA
Cell Differentiation
Immunohistochemistry
Breast Neoplasms

Keywords

  • Apoptosis
  • Bcl-2
  • Breast carcinoma
  • Estrogen receptor
  • Infiltrative ductal carcinoma
  • Intraductal carcinoma (ductal carcinoma in situ)
  • MIB-1
  • p53
  • Progesterone receptor
  • TUNEL

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Shen, Kuo Liang; Harn, Horng Jyh; Ho, Li Ing; Yu, Cheng Ping; Chiu, Shao Chih; Lee, Wei Hwa.

In: Cancer, Vol. 82, No. 12, 15.06.1998, p. 2373-2381.

Research output: Contribution to journalArticle

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title = "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",
abstract = "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.",
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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 - p53

KW - Progesterone receptor

KW - TUNEL

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