Is a Five Marker Panel with Basal Marker Expression (EGFR and/or CK5/6) Superior to a Three Marker Panel in Predicting Prognosis in Molecular Subtypes of Breast Carcinoma? A Comparative Study

Abstract

Breast cancer exhibits significant heterogeneity, as evidenced by the fact that tumours with similar morphologic and immunohistochemical features exhibit distinct clinical behaviour and response to therapy. This paved the way for microarray-based global gene expression profiling (GEP) and new approaches to classifying breast cancer into molecular subtypes. The triple negative phenotype has been identified as the worst prognosis group among all molecular subtypes (TN).Within this group, basal-like breast cancer (BLBC) was detected using a 5-marker surrogate panel that included ER-PR-HER2–negative and basal markers, such as epidermal growth factor receptor (EGFR) or Cytokeratin 5/6 (CK5/6) positive. The basal-like subtype, which accounts for 15 to 20% of all breast malignancies, is particularly important since it has a very bad prognosis.    EGFR and CK 5/6 are readily available and specific IHC surrogate basal markers that can be easily included in a five marker panel for breast cancer prognosis.BME is not only found in triple negative subtypes, but also in other molecular subtypes. Using IHC surrogate classification, 106 cases of invasive breast carcinoma with detailed clinical and histological prognostic factors were classified into molecular phenotypes. Tumors expressing the basal markers CK5/6 and EGFR were defined as basal marker expressing (BME) tumours, and they were compared to tumours expressing ER, PR, Her-2/neu, and triple negative tumours. These tumours were compared to invasive breast cancer prognostic and predictive markers. BME was found in 50 of the 106 cases. In addition, BME was linked to tumour necrosis, lymph node metastases, and a high histological grade.BME is an independent prognostic marker in breast carcinomas, and its expression is not confined to triple negative instances. Three panel markers had less prognostic significance than an enlarged surrogate panel comprising ER, PR, Her-2 neu, EGFR, and CK 5/6.