Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

-The pioneering works on molecular classification (MC) by Perou and Sorlie et al in the early 2000s using global gene expression profiling identified 5 intrinsic subtypes of invasive breast cancers (IBCs): luminal A, luminal B, normal breast-like, HER2-enriched, and basal-like subtypes, each unique in incidence, survival, and response to therapy. Because the application of gene expression profiling in daily practice is not economical or practical at the present time, many investigators have studied the use of immunohistochemical (IHC) surrogates as a substitute for determining the MC of IBC.

-To discuss the continuing efforts that have been made to develop clinically significant and readily available IHC surrogates for the MC of IBC.

-Data were obtained from pertinent peer-reviewed English-language literature.

-The most commonly used IHC surrogates are estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2), dividing IBC into luminal, HER2, and triple-negative subtypes. The addition of Ki-67, cytokeratin 5, and epidermal growth factor receptor (EGFR) separates luminal B from luminal A subtypes, and basal-like subtype from triple-negative breast cancer. More recently, biomarkers such as androgen receptor and p53 have been shown to further stratify these molecular subtypes. Although many studies of IHC-based MC have shown clinical significance similar to gene expression profiling-defined MC, its critical limitations are: (1) a lack of standardization in terminology, (2) a lack of standardization in biomarkers used for each subtype, and (3) the lack of a uniform cutoff for each biomarker. A panel of IHC surrogates for each subtype of IBC is proposed.