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Background <p>In clinical practice, breast cancer (BC) diagnosis traditionally relies on morphological analysis and the immunohistochemical (IHC) expression of markers such as ER, PR, HER2, and Ki67. However, these features do not fully capture the molecular subtypes identified through multi-gene expression profiling. The Prosigna PAM50 test, an FDA-approved prognostic tool, provides both recurrence risk and intrinsic tumor subtype classification.</p> Methods <p>We assessed the agreement between IHC-based classification and intrinsic molecular subtypes determined by Prosigna in a cohort of early-stage BC cases.</p> Results <p>A divergence between the two methods was observed in 34% of cases. Specifically, 26 cases initially classified as Luminal B by IHC were reclassified as Luminal A or HER2-enriched by PAM50, while 8 cases classified as Luminal A were redefined as Luminal B. This subtyping divergence was most frequent when the Ki67 IHC cut-off ranged from 21% to 25%, although a nearly substantial rate of divergence was also notably present in the adjacent 16–20% and 26–30% bands. These findings identify a broader borderline ‘grey zone’ between 16% and 30% where surrogate subtyping is least reproducible and molecular profiling provides the highest clinical utility.</p> Conclusions <p>The Prosigna test plays a valuable role in clinical practice for intrinsic BC classification, particularly in cases with borderline Ki67 levels. The involvement of a second pathologist and the use of digital Ki67 analysis may reduce reproducibility issues in surrogate subtyping, and Prosigna testing should be recommended in such cases.</p>

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Ki67 assessment, digital image analysis, and PAM50/Prosigna subtype divergence in early ER-positive breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月31日

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  • Federica Zito Marino,
  • Martina Amato,
  • Giuseppe D’abbronzo,
  • Alessandra Biasi,
  • Angela Ruggiero,
  • Grazia Arpino,
  • Mario Giuliano,
  • Carmine De Angelis,
  • Carminia Maria Della Corte,
  • Antonio Gambardella,
  • Michele Orditura,
  • Rosa Giannatiempo,
  • Marina Accardo,
  • Renato Franco

摘要

Background

In clinical practice, breast cancer (BC) diagnosis traditionally relies on morphological analysis and the immunohistochemical (IHC) expression of markers such as ER, PR, HER2, and Ki67. However, these features do not fully capture the molecular subtypes identified through multi-gene expression profiling. The Prosigna PAM50 test, an FDA-approved prognostic tool, provides both recurrence risk and intrinsic tumor subtype classification.

Methods

We assessed the agreement between IHC-based classification and intrinsic molecular subtypes determined by Prosigna in a cohort of early-stage BC cases.

Results

A divergence between the two methods was observed in 34% of cases. Specifically, 26 cases initially classified as Luminal B by IHC were reclassified as Luminal A or HER2-enriched by PAM50, while 8 cases classified as Luminal A were redefined as Luminal B. This subtyping divergence was most frequent when the Ki67 IHC cut-off ranged from 21% to 25%, although a nearly substantial rate of divergence was also notably present in the adjacent 16–20% and 26–30% bands. These findings identify a broader borderline ‘grey zone’ between 16% and 30% where surrogate subtyping is least reproducible and molecular profiling provides the highest clinical utility.

Conclusions

The Prosigna test plays a valuable role in clinical practice for intrinsic BC classification, particularly in cases with borderline Ki67 levels. The involvement of a second pathologist and the use of digital Ki67 analysis may reduce reproducibility issues in surrogate subtyping, and Prosigna testing should be recommended in such cases.