A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer

Birgitte Vrou Offersen; Jan Alsner; Karen Ege Olsen; Rikke Marianne Riisbro Sørensen; Nils Brunner; Flemming Brandt Sørensen; Boe Sandahl Sørensen; Birgitte Olrik Schlemmer; Jens Overgaard

doi:10.1080/02841860801958295

A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer

Birgitte Vrou Offersen, Jan Alsner, Karen Ege Olsen, Rikke Marianne Riisbro Sørensen, Nils Brunner, Flemming Brandt Sørensen, Boe Sandahl Sørensen, Birgitte Olrik Schlemmer, Jens Overgaard

23 Citationer (Scopus)

Abstract

BACKGROUND: The prognostic potential of HER2, TP53 mutations, PAI-1 protein levels, angiogenesis and proliferation were investigated in tumours from 408 patients with early breast cancer followed >10 years. One hundred and sixty seven patients (41%) died from breast cancer. MATERIALS AND METHODS: Tumour sections were stained for HER2, CD34, and MIB-1. HER2 scores were based on staining intensity, 3+ being considered HER2+. Angiogenesis was scored by the Chalkley method. MIB-1 was evaluated using systematic random sampling. PAI-1 was measured by ELISA. TP53 mutations were evaluated by DGGE analysis and DNA sequencing. RESULTS: Ninety one patients (22%) were HER2 positive. TP53 was mutated in 101 cases (25%). Median PAI-1, Chalkley and MIB-1 was 0.72 ng/mg protein (range, 0-90 ng/mg protein), 5.00 (range, 2.67-12.00) and 15% (range, 1-83%). MIB-1 was correlated with HER2+, Chalkley counts, TP53 mutations (all p <0.0001), and PAI-1 (p =0.002). In univariate analyses with DSS as endpoint, HER2+ (p <0.0001), mutated TP53 (p <0.0001), high Chalkley (p =0.008), MIB-1 (p =0.002), tumour size (p =0.008), grade (p <0.0001), negative estrogen receptor (p =0.0001), and lymph node status (p <0.0001) were prognostic markers. Among node-negative patients, HER2+ (p =0.0002), mutated TP53 (p =0.001), high PAI-1 levels (p =0.02), and grade (p =0.03) indicated poor DSS. In node-positive patients, HER2+ (p =0.0002), mutated TP53 (p <0.0001), MIB-1 (p =0.01), Chalkley scores (p =0.007), negative estrogen receptor (p <0.0001) and grade (p =0.001) indicated poor prognosis. In multivariate analysis, metastatic nodes (1-3 positive: RR 1.56 95% CI 1.02-2.38; >3 positive: RR 3.70 95% CI 2.54-5.38), HER2+ (RR 1.91, 95% CI 1.35-2.70), mutated TP53 (RR 1.70, 95% CI 1.21-2.38), PAI-1 (RR 1.04, 95% CI 1.01-1.07) and grade 3 (RR 1.96, 95% CI 1.83-3.22) were independent markers of poor outcome. CONCLUSION: Compared to PAI-1 protein levels, Chalkley counts and MIB-1, HER2+ and mutations of TP53 were the strongest independent markers of poor prognosis irrespective of nodal status.

Originalsprog	Engelsk
Tidsskrift	Acta Oncologica
Vol/bind	47
Udgave nummer	4
Sider (fra-til)	618-632
Antal sider	15
ISSN	0284-186X
DOI	https://doi.org/10.1080/02841860801958295
Status	Udgivet - 2008

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10.1080/02841860801958295

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Offersen, B. V., Alsner, J., Olsen, K. E., Sørensen, R. M. R., Brunner, N., Sørensen, F. B., Sørensen, B. S., Schlemmer, B. O., & Overgaard, J. (2008). A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer. Acta Oncologica, 47(4), 618-632. https://doi.org/10.1080/02841860801958295

A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer. / Offersen, Birgitte Vrou; Alsner, Jan; Olsen, Karen Ege et al.

I: Acta Oncologica, Bind 47, Nr. 4, 2008, s. 618-632.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Offersen, BV, Alsner, J, Olsen, KE, Sørensen, RMR, Brunner, N, Sørensen, FB, Sørensen, BS, Schlemmer, BO & Overgaard, J 2008, 'A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer', Acta Oncologica, bind 47, nr. 4, s. 618-632. https://doi.org/10.1080/02841860801958295

@article{9c025ba0bfbc11dd8e02000ea68e967b,

title = "A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer",

abstract = "BACKGROUND: The prognostic potential of HER2, TP53 mutations, PAI-1 protein levels, angiogenesis and proliferation were investigated in tumours from 408 patients with early breast cancer followed >10 years. One hundred and sixty seven patients (41%) died from breast cancer. MATERIALS AND METHODS: Tumour sections were stained for HER2, CD34, and MIB-1. HER2 scores were based on staining intensity, 3+ being considered HER2+. Angiogenesis was scored by the Chalkley method. MIB-1 was evaluated using systematic random sampling. PAI-1 was measured by ELISA. TP53 mutations were evaluated by DGGE analysis and DNA sequencing. RESULTS: Ninety one patients (22%) were HER2 positive. TP53 was mutated in 101 cases (25%). Median PAI-1, Chalkley and MIB-1 was 0.72 ng/mg protein (range, 0-90 ng/mg protein), 5.00 (range, 2.67-12.00) and 15% (range, 1-83%). MIB-1 was correlated with HER2+, Chalkley counts, TP53 mutations (all p <0.0001), and PAI-1 (p =0.002). In univariate analyses with DSS as endpoint, HER2+ (p <0.0001), mutated TP53 (p <0.0001), high Chalkley (p =0.008), MIB-1 (p =0.002), tumour size (p =0.008), grade (p <0.0001), negative estrogen receptor (p =0.0001), and lymph node status (p <0.0001) were prognostic markers. Among node-negative patients, HER2+ (p =0.0002), mutated TP53 (p =0.001), high PAI-1 levels (p =0.02), and grade (p =0.03) indicated poor DSS. In node-positive patients, HER2+ (p =0.0002), mutated TP53 (p <0.0001), MIB-1 (p =0.01), Chalkley scores (p =0.007), negative estrogen receptor (p <0.0001) and grade (p =0.001) indicated poor prognosis. In multivariate analysis, metastatic nodes (1-3 positive: RR 1.56 95% CI 1.02-2.38; >3 positive: RR 3.70 95% CI 2.54-5.38), HER2+ (RR 1.91, 95% CI 1.35-2.70), mutated TP53 (RR 1.70, 95% CI 1.21-2.38), PAI-1 (RR 1.04, 95% CI 1.01-1.07) and grade 3 (RR 1.96, 95% CI 1.83-3.22) were independent markers of poor outcome. CONCLUSION: Compared to PAI-1 protein levels, Chalkley counts and MIB-1, HER2+ and mutations of TP53 were the strongest independent markers of poor prognosis irrespective of nodal status.",

author = "Offersen, {Birgitte Vrou} and Jan Alsner and Olsen, {Karen Ege} and S{\o}rensen, {Rikke Marianne Riisbro} and Nils Brunner and S{\o}rensen, {Flemming Brandt} and S{\o}rensen, {Boe Sandahl} and Schlemmer, {Birgitte Olrik} and Jens Overgaard",

note = "Keywords: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cell Growth Processes; Female; Humans; Middle Aged; Mutation; Neoplasm Staging; Neovascularization, Pathologic; Plasminogen Activator Inhibitor 1; Receptor, erbB-2; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases",

year = "2008",

doi = "10.1080/02841860801958295",

language = "English",

volume = "47",

pages = "618--632",

journal = "Acta Oncologica, Supplement",

issn = "1100-1704",

publisher = "Taylor & Francis",

number = "4",

}

TY - JOUR

T1 - A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer

AU - Offersen, Birgitte Vrou

AU - Alsner, Jan

AU - Olsen, Karen Ege

AU - Sørensen, Rikke Marianne Riisbro

AU - Brunner, Nils

AU - Sørensen, Flemming Brandt

AU - Sørensen, Boe Sandahl

AU - Schlemmer, Birgitte Olrik

AU - Overgaard, Jens

N1 - Keywords: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cell Growth Processes; Female; Humans; Middle Aged; Mutation; Neoplasm Staging; Neovascularization, Pathologic; Plasminogen Activator Inhibitor 1; Receptor, erbB-2; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases

PY - 2008

Y1 - 2008

N2 - BACKGROUND: The prognostic potential of HER2, TP53 mutations, PAI-1 protein levels, angiogenesis and proliferation were investigated in tumours from 408 patients with early breast cancer followed >10 years. One hundred and sixty seven patients (41%) died from breast cancer. MATERIALS AND METHODS: Tumour sections were stained for HER2, CD34, and MIB-1. HER2 scores were based on staining intensity, 3+ being considered HER2+. Angiogenesis was scored by the Chalkley method. MIB-1 was evaluated using systematic random sampling. PAI-1 was measured by ELISA. TP53 mutations were evaluated by DGGE analysis and DNA sequencing. RESULTS: Ninety one patients (22%) were HER2 positive. TP53 was mutated in 101 cases (25%). Median PAI-1, Chalkley and MIB-1 was 0.72 ng/mg protein (range, 0-90 ng/mg protein), 5.00 (range, 2.67-12.00) and 15% (range, 1-83%). MIB-1 was correlated with HER2+, Chalkley counts, TP53 mutations (all p <0.0001), and PAI-1 (p =0.002). In univariate analyses with DSS as endpoint, HER2+ (p <0.0001), mutated TP53 (p <0.0001), high Chalkley (p =0.008), MIB-1 (p =0.002), tumour size (p =0.008), grade (p <0.0001), negative estrogen receptor (p =0.0001), and lymph node status (p <0.0001) were prognostic markers. Among node-negative patients, HER2+ (p =0.0002), mutated TP53 (p =0.001), high PAI-1 levels (p =0.02), and grade (p =0.03) indicated poor DSS. In node-positive patients, HER2+ (p =0.0002), mutated TP53 (p <0.0001), MIB-1 (p =0.01), Chalkley scores (p =0.007), negative estrogen receptor (p <0.0001) and grade (p =0.001) indicated poor prognosis. In multivariate analysis, metastatic nodes (1-3 positive: RR 1.56 95% CI 1.02-2.38; >3 positive: RR 3.70 95% CI 2.54-5.38), HER2+ (RR 1.91, 95% CI 1.35-2.70), mutated TP53 (RR 1.70, 95% CI 1.21-2.38), PAI-1 (RR 1.04, 95% CI 1.01-1.07) and grade 3 (RR 1.96, 95% CI 1.83-3.22) were independent markers of poor outcome. CONCLUSION: Compared to PAI-1 protein levels, Chalkley counts and MIB-1, HER2+ and mutations of TP53 were the strongest independent markers of poor prognosis irrespective of nodal status.

AB - BACKGROUND: The prognostic potential of HER2, TP53 mutations, PAI-1 protein levels, angiogenesis and proliferation were investigated in tumours from 408 patients with early breast cancer followed >10 years. One hundred and sixty seven patients (41%) died from breast cancer. MATERIALS AND METHODS: Tumour sections were stained for HER2, CD34, and MIB-1. HER2 scores were based on staining intensity, 3+ being considered HER2+. Angiogenesis was scored by the Chalkley method. MIB-1 was evaluated using systematic random sampling. PAI-1 was measured by ELISA. TP53 mutations were evaluated by DGGE analysis and DNA sequencing. RESULTS: Ninety one patients (22%) were HER2 positive. TP53 was mutated in 101 cases (25%). Median PAI-1, Chalkley and MIB-1 was 0.72 ng/mg protein (range, 0-90 ng/mg protein), 5.00 (range, 2.67-12.00) and 15% (range, 1-83%). MIB-1 was correlated with HER2+, Chalkley counts, TP53 mutations (all p <0.0001), and PAI-1 (p =0.002). In univariate analyses with DSS as endpoint, HER2+ (p <0.0001), mutated TP53 (p <0.0001), high Chalkley (p =0.008), MIB-1 (p =0.002), tumour size (p =0.008), grade (p <0.0001), negative estrogen receptor (p =0.0001), and lymph node status (p <0.0001) were prognostic markers. Among node-negative patients, HER2+ (p =0.0002), mutated TP53 (p =0.001), high PAI-1 levels (p =0.02), and grade (p =0.03) indicated poor DSS. In node-positive patients, HER2+ (p =0.0002), mutated TP53 (p <0.0001), MIB-1 (p =0.01), Chalkley scores (p =0.007), negative estrogen receptor (p <0.0001) and grade (p =0.001) indicated poor prognosis. In multivariate analysis, metastatic nodes (1-3 positive: RR 1.56 95% CI 1.02-2.38; >3 positive: RR 3.70 95% CI 2.54-5.38), HER2+ (RR 1.91, 95% CI 1.35-2.70), mutated TP53 (RR 1.70, 95% CI 1.21-2.38), PAI-1 (RR 1.04, 95% CI 1.01-1.07) and grade 3 (RR 1.96, 95% CI 1.83-3.22) were independent markers of poor outcome. CONCLUSION: Compared to PAI-1 protein levels, Chalkley counts and MIB-1, HER2+ and mutations of TP53 were the strongest independent markers of poor prognosis irrespective of nodal status.

U2 - 10.1080/02841860801958295

DO - 10.1080/02841860801958295

M3 - Journal article

C2 - 18465330

SN - 1100-1704

VL - 47

SP - 618

EP - 632

JO - Acta Oncologica, Supplement

JF - Acta Oncologica, Supplement

IS - 4

ER -

A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer

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