Posted on Nov 16, 2022

Evaluation of MKI67 mRNA quantitative analysis performance towards the distinction between the Luminal A and B molecular subtypes 

Regina Pinto1, Elsa Logarinho2, Ana Carmo Valente3 and Fernando Schmitt1,4

1 Ipatimup Diagnósticos,  Ipatimup, 4200-135 Porto, Portugal

2 i3S – Instituto de Investigação e Inovação em Saúde, 4200-135 Porto, Portugal

3 Serviço de Oncologia, Hospital de S. João – Porto, Portugal

4 Faculdade de Medicina, Universidade do Porto, Portugal

Traditionally, breast cancer prognosis is determined using immunohistochemistry (IHC). This is a staining process that enables pathologists to visualize proteins within cells that are important in the biologic pathways of breast cancer

However, with the development of genomics (the study of the genes in our DNA), molecular subtyping became available, enabling clinicians to better decide on the best treatment approach for patients.

There are at least four subgroups of breast cancer, luminal A, luminal B, HER-2 and triple negative. Working out which group a patient’s breast cancer falls within is important to estimate their risk of relapse as well as how well they are likely to respond to different therapies.

Being able to distinguish between aggressive luminal B cancers and less aggressive luminal A cancer, is particularly important for treatment planning. However, this relies on analysis of Ki-67 protein levels, this is a marker of proliferation, or how fast the cancer is likely to grow. Historically IHC has been poor at determining Ki-67 protein levels.

The MammaTyper® test is based on quantitative and standardized analysis of the four major biomarkers:

  • HER2 or ERBB2 (human epidermal growth factor receptor 2)
  • ER or ESR1 (estrogen receptor 1)
  • PR or PGR (progesterone receptor)
  • MKI67 (marker of proliferation Ki-67, a marker expressed in proliferating cells)

MammaTyper® has the potential to be as reliable as IHC but more accurate and faster, producing an efficient local laboratory result.

What did the researchers do?

In this study, researchers in Portugal led by Regina Pinto assessed breast cancer samples that had initially been sub-typed using IHC. However, where previous analysis had been inconclusive in determining for Ki-67. They compared these results with subtypes assessed by MammaTyper®.

They analysed 44 samples from biopsies taken from patients who were HER2 negative during 2019-20. HER2 negative means that they have low or no level of the protein HER2 on the surface of their cells.

What were the results?

IHC results for Ki-67 were all inconclusive within the range of 11%-28%. This means they were not giving an accurate estimation of Ki-67 which is important for distinguishing between luminal A and luminal B breast cancer, and therefore prognosis.

MammaTyper® results had a high level of positive agreement with IHC for the biomarkers ER, HER2 and PGR (91-98%). Showing it is a reliable test.

There was a lower level of agreement between IHC results and MammaTyper® for Ki67 (75%). However, IHC results for Ki67 were all inconclusive meaning that IHC was not a reliable way to determine Ki67 in these samples.

The authors concluded that the results indicated the potential superiority of MammaTyper® in being able to distinguish between the molecular subtypes luminal A from luminal B (HER2-negative) cancers.