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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 LU orcid ; Aaserud, Marit ; Sveli, My Anh Tu ; Borg, Åke LU ; Garred, Øystein ; Borgen, Elin and Naume, Bjørn , et al. (2021) In Cancers 13(23).
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 fea-tures, 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... (More)

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 fea-tures, 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 in-vestigate 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 macro-dissected 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 macro-dissected 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, intermedi-ate, 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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organization
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type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, Bulk, FFPE, Fresh-frozen, Macrodissection, PAM50, Prosigna, Risk of recurrence score
in
Cancers
volume
13
issue
23
article number
6118
publisher
MDPI AG
external identifiers
  • scopus:85120616067
  • pmid:34885228
ISSN
2072-6694
DOI
10.3390/cancers13236118
language
English
LU publication?
yes
id
fac8f3a4-29d4-461b-b3e6-241877dbda13
date added to LUP
2022-01-20 15:17:41
date last changed
2024-06-16 00:11:05
@article{fac8f3a4-29d4-461b-b3e6-241877dbda13,
  abstract     = {{<p>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 fea-tures, 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 in-vestigate 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 macro-dissected 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 macro-dissected 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, intermedi-ate, 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.</p>}},
  author       = {{Lien, Tonje G. and Ohnstad, Hege Oma and Lingjærde, Ole Christian and Vallon-Christersson, Johan and Aaserud, Marit and Sveli, My Anh Tu and Borg, Åke and Garred, Øystein and Borgen, Elin and Naume, Bjørn and Russnes, Hege and Sørlie, Therese}},
  issn         = {{2072-6694}},
  keywords     = {{Breast cancer; Bulk; FFPE; Fresh-frozen; Macrodissection; PAM50; Prosigna; Risk of recurrence score}},
  language     = {{eng}},
  number       = {{23}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Sample preparation approach influences pam50 risk of recurrence score in early breast cancer}},
  url          = {{http://dx.doi.org/10.3390/cancers13236118}},
  doi          = {{10.3390/cancers13236118}},
  volume       = {{13}},
  year         = {{2021}},
}