Ki67 assessment, digital image analysis, and PAM50/Prosigna subtype divergence in early ER-positive breast cancer.
9 affiliations
- 1Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
- 2Pathology Unit, Hospital University of Campania "Luigi Vanvitelli", Naples, Italy.
- 3Medical Oncology Unit "Santa Maria delle Grazie" Hospital, Pozzuoli, 80078, Naples, Italy.
- 4Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
- 5Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Napoli, Italy.
- 6Division of Medical Oncology, Department of Precision Medicine, School of Medicine, University of Campania "Luigi Vanvitelli", Via S. Pansini 5, 80131, Naples, Italy.
- 7Complex Operative Unit of Clinical Pathology, Betania Hospital, 80147, Naples, Italy.
- 8Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy. [email protected].
- 9Pathology Unit, Hospital University of Campania "Luigi Vanvitelli", Naples, Italy. [email protected].
Abstract
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.
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BibTeX
@article{marino2026ki67,
title = {{Ki67 assessment, digital image analysis, and PAM50/Prosigna subtype divergence in early ER-positive breast cancer.}},
author = {Federica Zito Marino and Martina Amato and Giuseppe D'abbronzo and Alessandra Biasi and Angela Ruggiero and Grazia Arpino and Mario Giuliano and Carmine De Angelis and Carminia Maria Della Corte and Antonio Gambardella and Michele Orditura and Rosa Giannatiempo and Marina Accardo and Renato Franco},
journal = {Journal of translational medicine},
year = {2026},
month = jul,
doi = {10.1186/s12967-026-08743-5},
url = {https://europepmc.org/article/MED/42958571},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Ki67 assessment, digital image analysis, and PAM50/Prosigna subtype divergence in early ER-positive breast cancer.
AU - Federica Zito Marino
AU - Martina Amato
AU - Giuseppe D'abbronzo
AU - Alessandra Biasi
AU - Angela Ruggiero
AU - Grazia Arpino
AU - Mario Giuliano
AU - Carmine De Angelis
AU - Carminia Maria Della Corte
AU - Antonio Gambardella
AU - Michele Orditura
AU - Rosa Giannatiempo
AU - Marina Accardo
AU - Renato Franco
PY - 2026
DA - 2026/07/31
JO - Journal of translational medicine
DO - 10.1186/s12967-026-08743-5
UR - https://europepmc.org/article/MED/42958571
AB - 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.
SN - 1479-5876
ER -