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Updated: May 7, 2025
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
Unlocking breast cancer in Brazilian public health system: Using tissue microarray for accurate immunohistochemical
Rubia Denise Ruppenthal1,2,3, Emily Ferreira Salles Pilar4, Jordan Boeira Dos Santos3
1Department of Pathology, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Background:
Breast cancer (BC) is a significant burden on healthcare systems, especially in low- and middle-income countries where access to diagnosis and treatment is challenging.
Objectives:
The purpose of this study was to assess the diagnostic accuracy and cost using tissue microarray (TMA) instead of traditional immunohistochemical (IHC) evaluation for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and the proliferation marker Ki-67 and BC subtyping within the Brazilian public health system.
Design:
This is a retrospective cohort study comparing TMA slides with traditional whole-slide evaluation for IHC markers in 242 BC cases.
Methods:
We used formalin-fixed tissue blocks for TMA assembly. Clinical data and IHC scores for ER, PR, HER2, and Ki-67 were obtained from pathology reports. Cohen's kappa (k) was used to assess TMA performance.
Results:
BC samples were distributed in 10 TMAs and 968 cores were scored (242 BC cases × 4 markers). In 97% of these, TMA reached high quality to adequate IHC scoring with minimal technical issues. Inter-examiner agreement was almost perfect for all markers (ranging from 0.85 for HER2 to 0.91 for ER, p < 0.001). The intratumoral heterogeneity ranged from almost perfect agreement for ER and HER2 to moderate to substantial for PR and Ki-67. TMA offers substantial time and cost savings, with an approximately 11-fold reduction compared to traditional methods. The concordance between TMA and original reports was almost perfect, with 93% overall agreement (k = 0.81, p < 0.001). However, TMA performance varied between markers, with intratumoral heterogeneity significantly impacting discordant results, particularly for Ki-67 and HER2. This ultimately affected the accuracy of BC subtyping. TMA performed well in identifying luminal A and triple-negative cases, but misclassification was common for luminal B and HER2-positive cases.
Conclusion:
TMA offers accurate and lower-cost results in the individualized IHC assessment of BC markers. However, we do not recommend the use of TMA in the subtyping of BC, where analysis of the whole section remains necessary for more accurate results. We advocate more studies using the TMA approach in the Brazilian public health system to advance women's health care.
