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Hopes and pitfalls of the molecular classification of breast cancer

Publication at Faculty of Medicine in Hradec Králové |
2015

Abstract

Results of the detection of hormone receptors, HER-2/neu, and Ki67 antigen are today an integral part of the histopathological diagnosis of breast cancer (BC). A critical factor for the success of these tests is the fulfillment of pre-analytical phase conditions, as well as taking into account the heterogeneous nature of the neoplastic population.

There are many efforts to include molecular characteristics of BC in tumor classification and prediction of results of treatment. Most of the work is based on the use of gene expression profiles.

Detection of expression of a large number of genes enables to find a set of genes correlating with the biological behavior of the tumor. Using this approach, four basic subgroups of BC have been identified - luminal, basal-like, HER-2 enriched and normal gland-like.

Over the course of time, the number of molecular categories has expanded - group of luminal BC has been subclassified into the luminal A, B and C. Also within basal-like BC additional subgroups have been identified.

However, the results of studies dealing with the analysis of gene expression profiles suggest that our understanding of the biology of breast cancer is far from being complete. The individual categories are defined differently in various publications and the comparison of results is very difficult.

Another approach is the immunohistochemical detection of various proteins as surrogate marker of the mRNA of individual genes. The advantage is the possibility to use archive materiál and lower costs.

Its main limitation is the inability of parallel detection of thousands of markers. The results of molecular classification are, however, not fundamentally surprising.

The fact that BC tumor stem cells can differentiate towards myoepithelial (or basal) and luminal cells has been known for a long time. Gene expression profiling has relatively quickly translated into clinical practice.

At present, several commercially available certified tests are available.