Cytological evaluation of biological prognostic markers from primary breast carcinomas

This study was undertaken to evaluate our ability to detect multiple molecular markers of prognosis and response to treatment in fine needle aspirates (FNA) from patients with primary breast carcinomas. 147 patients with operable primary breast carcinomas who had been recruited to a randomized trial...

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Published in:Breast cancer research and treatment Vol. 44; no. 1; pp. 65 - 74
Main Authors: Makris, A., Allred, D.C., Powles, T.J., Dowsett, M., Fernando, I.N., Trott, P.A., Ashley, S.E., Ormerod, M.G., Titley, J.C., Osborne, C.K.
Format: Journal Article
Language:English
Published: Dordrecht Springer 01.05.1997
Springer Nature B.V
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ISSN:0167-6806, 1573-7217
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Abstract This study was undertaken to evaluate our ability to detect multiple molecular markers of prognosis and response to treatment in fine needle aspirates (FNA) from patients with primary breast carcinomas. 147 patients with operable primary breast carcinomas who had been recruited to a randomized trial of primary medical therapy (PMT) versus adjuvant chemoendocrine therapy were analysed. FNAs were taken prior to therapy and from this multiple slides were produced using cytospin cytocentrifugation and stored at -80 degrees C for subsequent immunocytochemical analysis (ICA). ICA was performed for oestrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, and Bcl-2. Part of the aspirate was snap frozen and used for flow cytometric analysis of ploidy and S-phase fraction (SPF). In a subgroup of 50 patients who had surgery prior to systemic therapy, as well as FNAs, sections were also taken from paraffin-embedded blocks and stained by ICA for ER, PgR and p53 for validation. In these patients ER was additionally measured by enzyme immunoassay (EIA) from frozen tissue taken at surgery. ER, PgR, p53, Bcl-2, and Ki67 were successfully detected by ICA while ploidy and SPF were successfully measured by flow cytometry from FNA material. The percentage positive values obtained were reasonable and as follows: 74% for ER, 70% for PgR, 36% for p53, 80% for Bcl-2,68% of tumours were aneuploid and 32% diploid. Significant relationships between these measurements were observed in accordance with expectations. The concordance for ER, PgR, and p53 from FNA when compared to ICA of matching histological sections was 91.5%, 75.5%, and 75% respectively. For ER the concordance between measurement by ICA of cytological and histological samples and by EIA of frozen tissue was 82.5% and 84% respectively. These results indicate that multiple molecular markers can be adequately tested on cytological preparations from primary breast tumours. These markers can be used to determine prognosis and predict response to PMT.
AbstractList This study was undertaken to evaluate our ability to detect multiple molecular markers of prognosis and response to treatment in fine needle aspirates (FNA) from patients with primary breast carcinomas. 147 patients with operable primary breast carcinomas who had been recruited to a randomized trial of primary medical therapy (PMT) versus adjuvant chemoendocrine therapy were analysed. FNAs were taken prior to therapy and from this multiple slides were produced using cytospin cytocentrifugation and stored at -80 degrees C for subsequent immunocytochemical analysis (ICA). ICA was performed for oestrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, and Bcl-2. Part of the aspirate was snap frozen and used for flow cytometric analysis of ploidy and S-phase fraction (SPF). In a subgroup of 50 patients who had surgery prior to systemic therapy, as well as FNAs, sections were also taken from paraffin-embedded blocks and stained by ICA for ER, PgR and p53 for validation. In these patients ER was additionally measured by enzyme immunoassay (EIA) from frozen tissue taken at surgery. ER, PgR, p53, Bcl-2, and Ki67 were successfully detected by ICA while ploidy and SPF were successfully measured by flow cytometry from FNA material. The percentage positive values obtained were reasonable and as follows: 74% for ER, 70% for PgR, 36% for p53, 80% for Bcl-2,68% of tumours were aneuploid and 32% diploid. Significant relationships between these measurements were observed in accordance with expectations. The concordance for ER, PgR, and p53 from FNA when compared to ICA of matching histological sections was 91.5%, 75.5%, and 75% respectively. For ER the concordance between measurement by ICA of cytological and histological samples and by EIA of frozen tissue was 82.5% and 84% respectively. These results indicate that multiple molecular markers can be adequately tested on cytological preparations from primary breast tumours. These markers can be used to determine prognosis and predict response to PMT.
This study was undertaken to evaluate our ability to detect multiple molecular markers of prognosis and response to treatment in fine needle aspirates (FNA) from patients with primary breast carcinomas. 147 patients with operable primary breast carcinomas who had been recruited to a randomized trial of primary medical therapy (PMT) versus adjuvant chemoendocrine therapy were analysed. FNAs were taken prior to therapy and from this multiple slides were produced using cytospin cytocentrifugation and stored at -80 degrees C for subsequent immunocytochemical analysis (ICA). ICA was performed for oestrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, and Bcl-2. Part of the aspirate was snap frozen and used for flow cytometric analysis of ploidy and S-phase fraction (SPF). In a subgroup of 50 patients who had surgery prior to systemic therapy, as well as FNAs, sections were also taken from paraffin-embedded blocks and stained by ICA for ER, PgR and p53 for validation. In these patients ER was additionally measured by enzyme immunoassay (EIA) from frozen tissue taken at surgery. ER, PgR, p53, Bcl-2, and Ki67 were successfully detected by ICA while ploidy and SPF were successfully measured by flow cytometry from FNA material. The percentage positive values obtained were reasonable and as follows: 74% for ER, 70% for PgR, 36% for p53, 80% for Bcl-2,68% of tumours were aneuploid and 32% diploid. Significant relationships between these measurements were observed in accordance with expectations. The concordance for ER, PgR, and p53 from FNA when compared to ICA of matching histological sections was 91.5%, 75.5%, and 75% respectively. For ER the concordance between measurement by ICA of cytological and histological samples and by EIA of frozen tissue was 82.5% and 84% respectively. These results indicate that multiple molecular markers can be adequately tested on cytological preparations from primary breast tumours. These markers can be used to determine prognosis and predict response to PMT.This study was undertaken to evaluate our ability to detect multiple molecular markers of prognosis and response to treatment in fine needle aspirates (FNA) from patients with primary breast carcinomas. 147 patients with operable primary breast carcinomas who had been recruited to a randomized trial of primary medical therapy (PMT) versus adjuvant chemoendocrine therapy were analysed. FNAs were taken prior to therapy and from this multiple slides were produced using cytospin cytocentrifugation and stored at -80 degrees C for subsequent immunocytochemical analysis (ICA). ICA was performed for oestrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, and Bcl-2. Part of the aspirate was snap frozen and used for flow cytometric analysis of ploidy and S-phase fraction (SPF). In a subgroup of 50 patients who had surgery prior to systemic therapy, as well as FNAs, sections were also taken from paraffin-embedded blocks and stained by ICA for ER, PgR and p53 for validation. In these patients ER was additionally measured by enzyme immunoassay (EIA) from frozen tissue taken at surgery. ER, PgR, p53, Bcl-2, and Ki67 were successfully detected by ICA while ploidy and SPF were successfully measured by flow cytometry from FNA material. The percentage positive values obtained were reasonable and as follows: 74% for ER, 70% for PgR, 36% for p53, 80% for Bcl-2,68% of tumours were aneuploid and 32% diploid. Significant relationships between these measurements were observed in accordance with expectations. The concordance for ER, PgR, and p53 from FNA when compared to ICA of matching histological sections was 91.5%, 75.5%, and 75% respectively. For ER the concordance between measurement by ICA of cytological and histological samples and by EIA of frozen tissue was 82.5% and 84% respectively. These results indicate that multiple molecular markers can be adequately tested on cytological preparations from primary breast tumours. These markers can be used to determine prognosis and predict response to PMT.
This study was undertaken to evaluate our abilityto detect multiple molecular markers of prognosis andresponse to treatment in fine needle aspirates (FNA)from patients with primary breast carcinomas. 147 patientswith operable primary breast carcinomas who had beenrecruited to a randomized trial of primary medicaltherapy (PMT) versus adjuvant chemoendocrine therapy were analysed.FNAs were taken prior to therapy and fromthis multiple slides were produced using cytospin cytocentrifugationand stored at - 80 °C for subsequentimmunocytochemical analysis (ICA). ICA was performed for oestrogenreceptor (ER), progesterone receptor (PgR), p53, Ki67, andBcl-2. Part of the aspirate was snap frozenand used for flow cytometric analysis of ploidyand S-phase fraction (SPF). In a subgroup of50 patients who had surgery prior to systemictherapy, as well as FNAs, sections were alsotaken from paraffin-embedded blocks and stained by ICAfor ER, PgR and p53 for validation. Inthese patients ER was additionally measured by enzymeimmunoassay (EIA) from frozen tissue taken at surgery.ER, PgR, p53, Bcl-2, and Ki67 were successfullydetected by ICA while ploidy and SPF weresuccessfully measured by flow cytometry from FNA material.The percentage positive values obtained were reasonable andas follows: 74% for ER, 70% for PgR,36% for p53, 80% for Bcl-2. 68% oftumours were aneuploid and 32% diploid. Significant relationshipsbetween these measurements were observed in accordance withexpectations. The concordance for ER, PgR, and p53from FNA when compared to ICA of matchinghistological sections was 91.5%, 75.5%, and 75% respectively.For ER the concordance between measurement by ICAof cytological and histological samples and by EIAof frozen tissue was 82.5% and 84% respectively.These results indicate that multiple molecular markers canbe adequately tested on cytological preparations from primarybreast tumours. These markers can be used todetermine prognosis and predict response to PMT.[PUBLICATION ABSTRACT]
Author Allred, D.C.
Ashley, S.E.
Osborne, C.K.
Trott, P.A.
Ormerod, M.G.
Titley, J.C.
Powles, T.J.
Makris, A.
Fernando, I.N.
Dowsett, M.
Author_xml – sequence: 1
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  surname: Makris
  fullname: Makris, A.
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  givenname: D.C.
  surname: Allred
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  givenname: T.J.
  surname: Powles
  fullname: Powles, T.J.
– sequence: 4
  givenname: M.
  surname: Dowsett
  fullname: Dowsett, M.
– sequence: 5
  givenname: I.N.
  surname: Fernando
  fullname: Fernando, I.N.
– sequence: 6
  givenname: P.A.
  surname: Trott
  fullname: Trott, P.A.
– sequence: 7
  givenname: S.E.
  surname: Ashley
  fullname: Ashley, S.E.
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  surname: Ormerod
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  surname: Titley
  fullname: Titley, J.C.
– sequence: 10
  givenname: C.K.
  surname: Osborne
  fullname: Osborne, C.K.
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Issue 1
Keywords Human
Carcinoma
Prognosis
Conservation
Estrogen
Biological marker
Malignant tumor
Aspiration punction
Mammary gland diseases
Randomization
TP53 Gene
Fine needle
Mammary gland
Progesterone
Onc gene
Tumor suppressor gene
Hormonal receptor
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PublicationTitle Breast cancer research and treatment
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Snippet This study was undertaken to evaluate our ability to detect multiple molecular markers of prognosis and response to treatment in fine needle aspirates (FNA)...
This study was undertaken to evaluate our abilityto detect multiple molecular markers of prognosis andresponse to treatment in fine needle aspirates (FNA)from...
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StartPage 65
SubjectTerms Adult
Aged
Analysis of Variance
Biological and medical sciences
Biomarkers, Tumor - analysis
Biomarkers, Tumor - metabolism
Biopsy, Needle - methods
Biopsy, Needle - standards
Breast cancer
Breast Neoplasms - chemistry
Breast Neoplasms - diagnosis
Cancer research
Centrifugation
Cytodiagnosis - methods
Cytodiagnosis - standards
Female
Flow Cytometry - methods
Flow Cytometry - standards
Genetics
Gynecology. Andrology. Obstetrics
Humans
Immunoenzyme Techniques - standards
Immunohistochemistry
Ki-67 Antigen - analysis
Mammary gland diseases
Medical sciences
Middle Aged
Prognosis
Proto-Oncogene Proteins c-bcl-2 - analysis
Receptors, Estrogen - analysis
Receptors, Estrogen - metabolism
Receptors, Progesterone - analysis
Receptors, Progesterone - metabolism
Tumor Suppressor Protein p53 - analysis
Tumors
Title Cytological evaluation of biological prognostic markers from primary breast carcinomas
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