Accumulation of p53 tumor suppressor gene protein

An independent marker of prognosis in breast cancers

Ann D. Thor, Dan H. Moore, Susan M. Edgerton, Ernest S. Kawasaki, Ellen Reihsaus, Henry T. Lynch, Joseph N. Marcus, Laurent Schwartz, Ling Chun Chen, Brian H. Mayall, Helene S. Smith

Research output: Contribution to journalArticle

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Abstract

Background: Mutations of the tumor suppressor gene p53 have been identified in breast cancer cell lines, and some breast carcinomas are detectable by immunohistochemical assay because of p53 protein accumulation. Purpose: This study was designed to determine whether p53 protein accumulation in breast cancers correlates with p53 gene mutation, with survival, and with five pathobiologic factors associated with prognosis. Methods: IgGl monoclonal antibody to human p53 protein (PAb 1801) and immunohistochemical methods were used to detect p53 protein accumulation in archival formalin-fixed, paraffin-embedded, randomly selected carcinomas. We studied 295 invasive ductal carcinomas from the Massachusetts General Hospital; 151 were determined to be sporadic (not hereditary). We also studied 97 invasive ductal carcinomas-21 sporadic and 76 familial (hereditary)-from Creighton University. In addition, we examined 31 archival in situ carcinomas, 15 snap-frozen invasive ductal carcinomas, primary cell cultures from three benign breast tissue samples, and breast carcinoma cell lines MDA-MB-231 and MDA-MB-468. Results: Nuclear p53 protein was observed in 16% of the 31 in situ carcinomas, 22% of the 172 sporadic carcinomas, 34% of the 50 tumors from patients with familial breast cancer, 52% of the 23 tumors from patients with the familial breast and ovarian cancer syndrome, and all three tumors from two patients with the Li-Fraumeni syndrome. There was complete concordance between p53 gene mutation and p53 protein accumulation in the 15 snap-frozen carcinomas and in both breast carcinoma cell lines. Statistically significant associations of p53 protein accumulation with estrogen receptor negativity and with high nuclear grade were found. There were statistically significant associations, independent of other prognostic factors, between p53 protein accumulation and metastasis-free and overall survival, for randomly accrued and for both sporadic and familial tumors. Conclusions: Immu-nohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation. [J Natl Cancer Inst 84: 845-855, 1992]

Original languageEnglish
Pages (from-to)845-855
Number of pages11
JournalJournal of the National Cancer Institute
Volume84
Issue number11
DOIs
StatePublished - Jun 3 1992

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Tumor Suppressor Proteins
Prognosis
Tumor Suppressor Genes
Breast Cancer
Tumors
Tumor
Genes
Breast Neoplasms
Gene
Proteins
Protein
Ductal Carcinoma
Carcinoma
p53 Genes
Mutation
Survival
Carcinoma in Situ
Cells
Neoplasms
Cell Line

All Science Journal Classification (ASJC) codes

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging
  • Oncology
  • Cancer Research

Cite this

Accumulation of p53 tumor suppressor gene protein : An independent marker of prognosis in breast cancers. / Thor, Ann D.; Moore, Dan H.; Edgerton, Susan M.; Kawasaki, Ernest S.; Reihsaus, Ellen; Lynch, Henry T.; Marcus, Joseph N.; Schwartz, Laurent; Chen, Ling Chun; Mayall, Brian H.; Smith, Helene S.

In: Journal of the National Cancer Institute, Vol. 84, No. 11, 03.06.1992, p. 845-855.

Research output: Contribution to journalArticle

Thor, AD, Moore, DH, Edgerton, SM, Kawasaki, ES, Reihsaus, E, Lynch, HT, Marcus, JN, Schwartz, L, Chen, LC, Mayall, BH & Smith, HS 1992, 'Accumulation of p53 tumor suppressor gene protein: An independent marker of prognosis in breast cancers', Journal of the National Cancer Institute, vol. 84, no. 11, pp. 845-855. https://doi.org/10.1093/jnci/84.11.845
Thor, Ann D. ; Moore, Dan H. ; Edgerton, Susan M. ; Kawasaki, Ernest S. ; Reihsaus, Ellen ; Lynch, Henry T. ; Marcus, Joseph N. ; Schwartz, Laurent ; Chen, Ling Chun ; Mayall, Brian H. ; Smith, Helene S. / Accumulation of p53 tumor suppressor gene protein : An independent marker of prognosis in breast cancers. In: Journal of the National Cancer Institute. 1992 ; Vol. 84, No. 11. pp. 845-855.
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abstract = "Background: Mutations of the tumor suppressor gene p53 have been identified in breast cancer cell lines, and some breast carcinomas are detectable by immunohistochemical assay because of p53 protein accumulation. Purpose: This study was designed to determine whether p53 protein accumulation in breast cancers correlates with p53 gene mutation, with survival, and with five pathobiologic factors associated with prognosis. Methods: IgGl monoclonal antibody to human p53 protein (PAb 1801) and immunohistochemical methods were used to detect p53 protein accumulation in archival formalin-fixed, paraffin-embedded, randomly selected carcinomas. We studied 295 invasive ductal carcinomas from the Massachusetts General Hospital; 151 were determined to be sporadic (not hereditary). We also studied 97 invasive ductal carcinomas-21 sporadic and 76 familial (hereditary)-from Creighton University. In addition, we examined 31 archival in situ carcinomas, 15 snap-frozen invasive ductal carcinomas, primary cell cultures from three benign breast tissue samples, and breast carcinoma cell lines MDA-MB-231 and MDA-MB-468. Results: Nuclear p53 protein was observed in 16{\%} of the 31 in situ carcinomas, 22{\%} of the 172 sporadic carcinomas, 34{\%} of the 50 tumors from patients with familial breast cancer, 52{\%} of the 23 tumors from patients with the familial breast and ovarian cancer syndrome, and all three tumors from two patients with the Li-Fraumeni syndrome. There was complete concordance between p53 gene mutation and p53 protein accumulation in the 15 snap-frozen carcinomas and in both breast carcinoma cell lines. Statistically significant associations of p53 protein accumulation with estrogen receptor negativity and with high nuclear grade were found. There were statistically significant associations, independent of other prognostic factors, between p53 protein accumulation and metastasis-free and overall survival, for randomly accrued and for both sporadic and familial tumors. Conclusions: Immu-nohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation. [J Natl Cancer Inst 84: 845-855, 1992]",
author = "Thor, {Ann D.} and Moore, {Dan H.} and Edgerton, {Susan M.} and Kawasaki, {Ernest S.} and Ellen Reihsaus and Lynch, {Henry T.} and Marcus, {Joseph N.} and Laurent Schwartz and Chen, {Ling Chun} and Mayall, {Brian H.} and Smith, {Helene S.}",
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T1 - Accumulation of p53 tumor suppressor gene protein

T2 - An independent marker of prognosis in breast cancers

AU - Thor, Ann D.

AU - Moore, Dan H.

AU - Edgerton, Susan M.

AU - Kawasaki, Ernest S.

AU - Reihsaus, Ellen

AU - Lynch, Henry T.

AU - Marcus, Joseph N.

AU - Schwartz, Laurent

AU - Chen, Ling Chun

AU - Mayall, Brian H.

AU - Smith, Helene S.

PY - 1992/6/3

Y1 - 1992/6/3

N2 - Background: Mutations of the tumor suppressor gene p53 have been identified in breast cancer cell lines, and some breast carcinomas are detectable by immunohistochemical assay because of p53 protein accumulation. Purpose: This study was designed to determine whether p53 protein accumulation in breast cancers correlates with p53 gene mutation, with survival, and with five pathobiologic factors associated with prognosis. Methods: IgGl monoclonal antibody to human p53 protein (PAb 1801) and immunohistochemical methods were used to detect p53 protein accumulation in archival formalin-fixed, paraffin-embedded, randomly selected carcinomas. We studied 295 invasive ductal carcinomas from the Massachusetts General Hospital; 151 were determined to be sporadic (not hereditary). We also studied 97 invasive ductal carcinomas-21 sporadic and 76 familial (hereditary)-from Creighton University. In addition, we examined 31 archival in situ carcinomas, 15 snap-frozen invasive ductal carcinomas, primary cell cultures from three benign breast tissue samples, and breast carcinoma cell lines MDA-MB-231 and MDA-MB-468. Results: Nuclear p53 protein was observed in 16% of the 31 in situ carcinomas, 22% of the 172 sporadic carcinomas, 34% of the 50 tumors from patients with familial breast cancer, 52% of the 23 tumors from patients with the familial breast and ovarian cancer syndrome, and all three tumors from two patients with the Li-Fraumeni syndrome. There was complete concordance between p53 gene mutation and p53 protein accumulation in the 15 snap-frozen carcinomas and in both breast carcinoma cell lines. Statistically significant associations of p53 protein accumulation with estrogen receptor negativity and with high nuclear grade were found. There were statistically significant associations, independent of other prognostic factors, between p53 protein accumulation and metastasis-free and overall survival, for randomly accrued and for both sporadic and familial tumors. Conclusions: Immu-nohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation. [J Natl Cancer Inst 84: 845-855, 1992]

AB - Background: Mutations of the tumor suppressor gene p53 have been identified in breast cancer cell lines, and some breast carcinomas are detectable by immunohistochemical assay because of p53 protein accumulation. Purpose: This study was designed to determine whether p53 protein accumulation in breast cancers correlates with p53 gene mutation, with survival, and with five pathobiologic factors associated with prognosis. Methods: IgGl monoclonal antibody to human p53 protein (PAb 1801) and immunohistochemical methods were used to detect p53 protein accumulation in archival formalin-fixed, paraffin-embedded, randomly selected carcinomas. We studied 295 invasive ductal carcinomas from the Massachusetts General Hospital; 151 were determined to be sporadic (not hereditary). We also studied 97 invasive ductal carcinomas-21 sporadic and 76 familial (hereditary)-from Creighton University. In addition, we examined 31 archival in situ carcinomas, 15 snap-frozen invasive ductal carcinomas, primary cell cultures from three benign breast tissue samples, and breast carcinoma cell lines MDA-MB-231 and MDA-MB-468. Results: Nuclear p53 protein was observed in 16% of the 31 in situ carcinomas, 22% of the 172 sporadic carcinomas, 34% of the 50 tumors from patients with familial breast cancer, 52% of the 23 tumors from patients with the familial breast and ovarian cancer syndrome, and all three tumors from two patients with the Li-Fraumeni syndrome. There was complete concordance between p53 gene mutation and p53 protein accumulation in the 15 snap-frozen carcinomas and in both breast carcinoma cell lines. Statistically significant associations of p53 protein accumulation with estrogen receptor negativity and with high nuclear grade were found. There were statistically significant associations, independent of other prognostic factors, between p53 protein accumulation and metastasis-free and overall survival, for randomly accrued and for both sporadic and familial tumors. Conclusions: Immu-nohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation. [J Natl Cancer Inst 84: 845-855, 1992]

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