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Sample Preparation Approach Influences PAM50 Risk of Recurrence Score in Early Breast Cancer

SIMPLE SUMMARY: The PAM50 risk of recurrence (ROR) score is predictive of the risk of distant recurrence and the benefits of adjuvant therapy in early breast cancer. The Prosigna assay utilizes RNA from tumor cells selected via macrodissection of formalin-fixed, paraffin-embedded (FFPE) tissue secti...

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Autores principales: Lien, Tonje G., Ohnstad, Hege Oma, Lingjærde, Ole Christian, Vallon-Christersson, Johan, Aaserud, Marit, Sveli, My Anh Tu, Borg, Åke, OSBREAC, on behalf of, Garred, Øystein, Borgen, Elin, Naume, Bjørn, Russnes, Hege, Sørlie, Therese
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657125/
https://www.ncbi.nlm.nih.gov/pubmed/34885228
http://dx.doi.org/10.3390/cancers13236118
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author Lien, Tonje G.
Ohnstad, Hege Oma
Lingjærde, Ole Christian
Vallon-Christersson, Johan
Aaserud, Marit
Sveli, My Anh Tu
Borg, Åke
OSBREAC, on behalf of
Garred, Øystein
Borgen, Elin
Naume, Bjørn
Russnes, Hege
Sørlie, Therese
author_facet Lien, Tonje G.
Ohnstad, Hege Oma
Lingjærde, Ole Christian
Vallon-Christersson, Johan
Aaserud, Marit
Sveli, My Anh Tu
Borg, Åke
OSBREAC, on behalf of
Garred, Øystein
Borgen, Elin
Naume, Bjørn
Russnes, Hege
Sørlie, Therese
author_sort Lien, Tonje G.
collection PubMed
description SIMPLE SUMMARY: The PAM50 risk of recurrence (ROR) score is predictive of the risk of distant recurrence and the benefits of adjuvant therapy in early breast cancer. The Prosigna assay utilizes RNA from tumor cells selected via macrodissection of formalin-fixed, paraffin-embedded (FFPE) tissue sections to measure the activity of the PAM50 genes. An alternative and widely used extraction method is RNA purification from fresh-frozen (FF) bulk tissue without enriching the tumor cellularity. However, the impact of the RNA preparation approach on ROR scores and subsequent treatment selection has not been systematically evaluated. We compared the different approaches and found high correlation between risk of recurrence scores estimated from macrodissected FFPE tissue and scores estimated from bulk FF tumor tissue. However, important discrepancies were revealed for luminal tumors, which may have consequences for treatment recommendations for these patients. ABSTRACT: The PAM50 gene expression subtypes and the associated risk of recurrence (ROR) score are used to predict the risk of recurrence and the benefits of adjuvant therapy in early-stage breast cancer. The Prosigna assay includes the PAM50 subtypes along with their clinicopathological features, and is approved for treatment recommendations for adjuvant hormonal therapy and chemotherapy in hormone-receptor-positive early breast cancer. The Prosigna test utilizes RNA extracted from macrodissected tumor cells obtained from formalin-fixed, paraffin-embedded (FFPE) tissue sections. However, RNA extracted from fresh-frozen (FF) bulk tissue without macrodissection is widely used for research purposes, and yields high-quality RNA for downstream analyses. To investigate the impact of the sample preparation approach on ROR scores, we analyzed 94 breast carcinomas included in an observational study that had available gene expression data from macrodissected FFPE tissue and FF bulk tumor tissue, along with the clinically approved Prosigna scores for the node-negative, hormone-receptor-positive, HER2-negative cases (n = 54). ROR scores were calculated in R; the resulting two sets of scores from FFPE and FF samples were compared, and treatment recommendations were evaluated. Overall, ROR scores calculated based on the macrodissected FFPE tissue were consistent with the Prosigna scores. However, analyses from bulk tissue yielded a higher proportion of cases classified as normal-like; these were samples with relatively low tumor cellularity, leading to lower ROR scores. When comparing ROR scores (low, intermediate, and high), discordant cases between the two preparation approaches were revealed among the luminal tumors; the recommended treatment would have changed in a minority of cases.
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spelling pubmed-86571252021-12-10 Sample Preparation Approach Influences PAM50 Risk of Recurrence Score in Early Breast Cancer Lien, Tonje G. Ohnstad, Hege Oma Lingjærde, Ole Christian Vallon-Christersson, Johan Aaserud, Marit Sveli, My Anh Tu Borg, Åke OSBREAC, on behalf of Garred, Øystein Borgen, Elin Naume, Bjørn Russnes, Hege Sørlie, Therese Cancers (Basel) Article SIMPLE SUMMARY: The PAM50 risk of recurrence (ROR) score is predictive of the risk of distant recurrence and the benefits of adjuvant therapy in early breast cancer. The Prosigna assay utilizes RNA from tumor cells selected via macrodissection of formalin-fixed, paraffin-embedded (FFPE) tissue sections to measure the activity of the PAM50 genes. An alternative and widely used extraction method is RNA purification from fresh-frozen (FF) bulk tissue without enriching the tumor cellularity. However, the impact of the RNA preparation approach on ROR scores and subsequent treatment selection has not been systematically evaluated. We compared the different approaches and found high correlation between risk of recurrence scores estimated from macrodissected FFPE tissue and scores estimated from bulk FF tumor tissue. However, important discrepancies were revealed for luminal tumors, which may have consequences for treatment recommendations for these patients. ABSTRACT: The PAM50 gene expression subtypes and the associated risk of recurrence (ROR) score are used to predict the risk of recurrence and the benefits of adjuvant therapy in early-stage breast cancer. The Prosigna assay includes the PAM50 subtypes along with their clinicopathological features, and is approved for treatment recommendations for adjuvant hormonal therapy and chemotherapy in hormone-receptor-positive early breast cancer. The Prosigna test utilizes RNA extracted from macrodissected tumor cells obtained from formalin-fixed, paraffin-embedded (FFPE) tissue sections. However, RNA extracted from fresh-frozen (FF) bulk tissue without macrodissection is widely used for research purposes, and yields high-quality RNA for downstream analyses. To investigate the impact of the sample preparation approach on ROR scores, we analyzed 94 breast carcinomas included in an observational study that had available gene expression data from macrodissected FFPE tissue and FF bulk tumor tissue, along with the clinically approved Prosigna scores for the node-negative, hormone-receptor-positive, HER2-negative cases (n = 54). ROR scores were calculated in R; the resulting two sets of scores from FFPE and FF samples were compared, and treatment recommendations were evaluated. Overall, ROR scores calculated based on the macrodissected FFPE tissue were consistent with the Prosigna scores. However, analyses from bulk tissue yielded a higher proportion of cases classified as normal-like; these were samples with relatively low tumor cellularity, leading to lower ROR scores. When comparing ROR scores (low, intermediate, and high), discordant cases between the two preparation approaches were revealed among the luminal tumors; the recommended treatment would have changed in a minority of cases. MDPI 2021-12-04 /pmc/articles/PMC8657125/ /pubmed/34885228 http://dx.doi.org/10.3390/cancers13236118 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lien, Tonje G.
Ohnstad, Hege Oma
Lingjærde, Ole Christian
Vallon-Christersson, Johan
Aaserud, Marit
Sveli, My Anh Tu
Borg, Åke
OSBREAC, on behalf of
Garred, Øystein
Borgen, Elin
Naume, Bjørn
Russnes, Hege
Sørlie, Therese
Sample Preparation Approach Influences PAM50 Risk of Recurrence Score in Early Breast Cancer
title Sample Preparation Approach Influences PAM50 Risk of Recurrence Score in Early Breast Cancer
title_full Sample Preparation Approach Influences PAM50 Risk of Recurrence Score in Early Breast Cancer
title_fullStr Sample Preparation Approach Influences PAM50 Risk of Recurrence Score in Early Breast Cancer
title_full_unstemmed Sample Preparation Approach Influences PAM50 Risk of Recurrence Score in Early Breast Cancer
title_short Sample Preparation Approach Influences PAM50 Risk of Recurrence Score in Early Breast Cancer
title_sort sample preparation approach influences pam50 risk of recurrence score in early breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657125/
https://www.ncbi.nlm.nih.gov/pubmed/34885228
http://dx.doi.org/10.3390/cancers13236118
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