Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases

Olufunmilayo I. Olopade, Moses O. Adeyanju, Ahmad Safa, Fitsum Hagos, Rosemarie Mick, Craig B. Thompson, Wendy M. Recant

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

PURPOSE: Dysregulation of genes that control apoptosis can contribute to tumor progression and increased drug resistance. The BCL2 gene and its family member BCL-x as well as the TP53 genes regulate apoptosis and have been shown to have a direct effect on the sensitivity of cancer cells to radiation and chemotherapeutic agents. METHODS: The expression of BCL-x, a BCL2-related protein that is a potent inhibitor of apoptosis, was investigated by immunohistochemical and immunoblot methods in 43 primary untreated breast carcinomas, in conjunction with BCL2 and TP53. RESULTS: BCL-x protein was overexpressed in 18 of 42 (43%) invasive breast cancers when compared with adjacent normal breast epithelium. Western blot analysis of eight primary breast cancers and five breast cancer cell lines indicated that BCL-x(L) was the predominant BCL-x protein expressed. Overexpression of BCL-x protein in these tumors was associated with higher tumor grade and increased number of positive nodes. In contrast, BCL2 protein was overexpressed in 19 of 42 tumors (45%) and was strongly correlated with estrogen receptor positivity, lower tumor grade, smaller tumor size, and lower stage. TP53 protein immunostaining was detected in 12 of 40 tumors (29%) and was inversely correlated with BCL2 expression and ER positivity. There was no correlation between the level of BCL-x protein expression and age, tumor size, ER status, and TP53 status. At a median follow-up time of 216 weeks, there was a trend toward decreased overall survival in patients with tumors overexpressing BCL- x. CONCLUSIONS: These findings suggest that expression of BCL-x protein is increased in a significant fraction of invasive breast cancers. In contrast to BCL2 expression, up-regulation of BCL-x protein may be a marker of tumor progression. Additional data including larger numbers of patients, more uniform treatments, and longer follow-up are needed to define the prognostic significance of overexpression of BCL-x during breast cancer progression.

Original languageEnglish (US)
Pages (from-to)230-237
Number of pages8
JournalCancer Journal from Scientific American
Volume3
Issue number4
StatePublished - 1997
Externally publishedYes

Fingerprint

Breast Neoplasms
Neoplasm Metastasis
Neoplasms
Proteins
Proto-Oncogene Proteins c-bcl-2
Apoptosis
Tumor Suppressor Protein p53
p53 Genes
Tumor Biomarkers
Drug Resistance
Estrogen Receptors
Genes
Breast
Up-Regulation
Epithelium
Western Blotting
Radiation
Cell Line
Survival

Keywords

  • Apoptosis
  • BCL-x
  • BCL2
  • Breast cancer
  • Drug resistance
  • TP53

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Olopade, O. I., Adeyanju, M. O., Safa, A., Hagos, F., Mick, R., Thompson, C. B., & Recant, W. M. (1997). Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases. Cancer Journal from Scientific American, 3(4), 230-237.

Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases. / Olopade, Olufunmilayo I.; Adeyanju, Moses O.; Safa, Ahmad; Hagos, Fitsum; Mick, Rosemarie; Thompson, Craig B.; Recant, Wendy M.

In: Cancer Journal from Scientific American, Vol. 3, No. 4, 1997, p. 230-237.

Research output: Contribution to journalArticle

Olopade, OI, Adeyanju, MO, Safa, A, Hagos, F, Mick, R, Thompson, CB & Recant, WM 1997, 'Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases', Cancer Journal from Scientific American, vol. 3, no. 4, pp. 230-237.
Olopade, Olufunmilayo I. ; Adeyanju, Moses O. ; Safa, Ahmad ; Hagos, Fitsum ; Mick, Rosemarie ; Thompson, Craig B. ; Recant, Wendy M. / Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases. In: Cancer Journal from Scientific American. 1997 ; Vol. 3, No. 4. pp. 230-237.
@article{3222308296354b9bb7cdc5f9cf7d7e6d,
title = "Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases",
abstract = "PURPOSE: Dysregulation of genes that control apoptosis can contribute to tumor progression and increased drug resistance. The BCL2 gene and its family member BCL-x as well as the TP53 genes regulate apoptosis and have been shown to have a direct effect on the sensitivity of cancer cells to radiation and chemotherapeutic agents. METHODS: The expression of BCL-x, a BCL2-related protein that is a potent inhibitor of apoptosis, was investigated by immunohistochemical and immunoblot methods in 43 primary untreated breast carcinomas, in conjunction with BCL2 and TP53. RESULTS: BCL-x protein was overexpressed in 18 of 42 (43{\%}) invasive breast cancers when compared with adjacent normal breast epithelium. Western blot analysis of eight primary breast cancers and five breast cancer cell lines indicated that BCL-x(L) was the predominant BCL-x protein expressed. Overexpression of BCL-x protein in these tumors was associated with higher tumor grade and increased number of positive nodes. In contrast, BCL2 protein was overexpressed in 19 of 42 tumors (45{\%}) and was strongly correlated with estrogen receptor positivity, lower tumor grade, smaller tumor size, and lower stage. TP53 protein immunostaining was detected in 12 of 40 tumors (29{\%}) and was inversely correlated with BCL2 expression and ER positivity. There was no correlation between the level of BCL-x protein expression and age, tumor size, ER status, and TP53 status. At a median follow-up time of 216 weeks, there was a trend toward decreased overall survival in patients with tumors overexpressing BCL- x. CONCLUSIONS: These findings suggest that expression of BCL-x protein is increased in a significant fraction of invasive breast cancers. In contrast to BCL2 expression, up-regulation of BCL-x protein may be a marker of tumor progression. Additional data including larger numbers of patients, more uniform treatments, and longer follow-up are needed to define the prognostic significance of overexpression of BCL-x during breast cancer progression.",
keywords = "Apoptosis, BCL-x, BCL2, Breast cancer, Drug resistance, TP53",
author = "Olopade, {Olufunmilayo I.} and Adeyanju, {Moses O.} and Ahmad Safa and Fitsum Hagos and Rosemarie Mick and Thompson, {Craig B.} and Recant, {Wendy M.}",
year = "1997",
language = "English (US)",
volume = "3",
pages = "230--237",
journal = "Cancer journal (Sudbury, Mass.)",
issn = "1528-9117",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases

AU - Olopade, Olufunmilayo I.

AU - Adeyanju, Moses O.

AU - Safa, Ahmad

AU - Hagos, Fitsum

AU - Mick, Rosemarie

AU - Thompson, Craig B.

AU - Recant, Wendy M.

PY - 1997

Y1 - 1997

N2 - PURPOSE: Dysregulation of genes that control apoptosis can contribute to tumor progression and increased drug resistance. The BCL2 gene and its family member BCL-x as well as the TP53 genes regulate apoptosis and have been shown to have a direct effect on the sensitivity of cancer cells to radiation and chemotherapeutic agents. METHODS: The expression of BCL-x, a BCL2-related protein that is a potent inhibitor of apoptosis, was investigated by immunohistochemical and immunoblot methods in 43 primary untreated breast carcinomas, in conjunction with BCL2 and TP53. RESULTS: BCL-x protein was overexpressed in 18 of 42 (43%) invasive breast cancers when compared with adjacent normal breast epithelium. Western blot analysis of eight primary breast cancers and five breast cancer cell lines indicated that BCL-x(L) was the predominant BCL-x protein expressed. Overexpression of BCL-x protein in these tumors was associated with higher tumor grade and increased number of positive nodes. In contrast, BCL2 protein was overexpressed in 19 of 42 tumors (45%) and was strongly correlated with estrogen receptor positivity, lower tumor grade, smaller tumor size, and lower stage. TP53 protein immunostaining was detected in 12 of 40 tumors (29%) and was inversely correlated with BCL2 expression and ER positivity. There was no correlation between the level of BCL-x protein expression and age, tumor size, ER status, and TP53 status. At a median follow-up time of 216 weeks, there was a trend toward decreased overall survival in patients with tumors overexpressing BCL- x. CONCLUSIONS: These findings suggest that expression of BCL-x protein is increased in a significant fraction of invasive breast cancers. In contrast to BCL2 expression, up-regulation of BCL-x protein may be a marker of tumor progression. Additional data including larger numbers of patients, more uniform treatments, and longer follow-up are needed to define the prognostic significance of overexpression of BCL-x during breast cancer progression.

AB - PURPOSE: Dysregulation of genes that control apoptosis can contribute to tumor progression and increased drug resistance. The BCL2 gene and its family member BCL-x as well as the TP53 genes regulate apoptosis and have been shown to have a direct effect on the sensitivity of cancer cells to radiation and chemotherapeutic agents. METHODS: The expression of BCL-x, a BCL2-related protein that is a potent inhibitor of apoptosis, was investigated by immunohistochemical and immunoblot methods in 43 primary untreated breast carcinomas, in conjunction with BCL2 and TP53. RESULTS: BCL-x protein was overexpressed in 18 of 42 (43%) invasive breast cancers when compared with adjacent normal breast epithelium. Western blot analysis of eight primary breast cancers and five breast cancer cell lines indicated that BCL-x(L) was the predominant BCL-x protein expressed. Overexpression of BCL-x protein in these tumors was associated with higher tumor grade and increased number of positive nodes. In contrast, BCL2 protein was overexpressed in 19 of 42 tumors (45%) and was strongly correlated with estrogen receptor positivity, lower tumor grade, smaller tumor size, and lower stage. TP53 protein immunostaining was detected in 12 of 40 tumors (29%) and was inversely correlated with BCL2 expression and ER positivity. There was no correlation between the level of BCL-x protein expression and age, tumor size, ER status, and TP53 status. At a median follow-up time of 216 weeks, there was a trend toward decreased overall survival in patients with tumors overexpressing BCL- x. CONCLUSIONS: These findings suggest that expression of BCL-x protein is increased in a significant fraction of invasive breast cancers. In contrast to BCL2 expression, up-regulation of BCL-x protein may be a marker of tumor progression. Additional data including larger numbers of patients, more uniform treatments, and longer follow-up are needed to define the prognostic significance of overexpression of BCL-x during breast cancer progression.

KW - Apoptosis

KW - BCL-x

KW - BCL2

KW - Breast cancer

KW - Drug resistance

KW - TP53

UR - http://www.scopus.com/inward/record.url?scp=0030805125&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030805125&partnerID=8YFLogxK

M3 - Article

VL - 3

SP - 230

EP - 237

JO - Cancer journal (Sudbury, Mass.)

JF - Cancer journal (Sudbury, Mass.)

SN - 1528-9117

IS - 4

ER -