p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas

Abstract

Human breast carcinomas represent a heterogeneous group of tumors diverse in behavior, outcome, and response to therapy. However, the current system of pathological classification does not take into account biologic determinants of prognosis. The purpose of this study was to classify and characterize breast carcinomas based on variations in protein expression patterns derived from immunohistochemical analyses on tissue microarrays (TMAs). Therefore, 11 TMAs representing 168 invasive breast carcinomas were constructed. Breast tumors were classified into four different subtypes depending on estrogen receptor (ER) and HER2 expression. Basal-type tumors expressed neither of these proteins and represented 7.6% of our series; basal-like HER2-overexpressing tumors did not express ER and represented 17.7%; luminal-type tumors expressed ER and represented 72.8% of this series (luminal A 56.3%, luminal B 16.5%). Moreover, we characterized each subtype based on P-cadherin (P-CD), p63, cytokeratin (CK)5, BCL2, and Ki67 expression. Basal-type tumors were mostly grade III, more frequently P-CD-, p63-, and CK5-positive, and had a high proliferation rate. Conversely, luminal-type tumors rarely expressed basal markers and had a low grade and proliferation rate. Basal-like HER2-overexpressing tumors showed a basal-type profile similar with a high grade and up-regulation of P-CD and CK5. With this study, we show that P-CD, p63, and CK5 are important molecular markers that can be used to distinguish a basal phenotype. In addition, we also demonstrate the usefulness of TMAs in breast carcinoma immunoprofiling.

Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile

“…Our study confirms and extends the previously reported findings of the basal-like carcinoma immunophenotype. [5][6][7][8]10 In addition, we demonstrate the presence of in situ carcinoma as the likely precursor lesion for invasive basal-like carcinoma.…”

“…5 The characteristic immunohistologic phenotype of these tumors is the 'triple negative' receptors of estrogen, progesterone and HER-2/neu, while expressing keratins CK5/6, CK14, CK17, vimentin and HER-1. [5][6][7][8][9][10][11] While the invasive basal-like neoplasms are reasonably well characterized morphologically and immunohistochemically, there is little data about the precursor lesion(s) for the entity.…”

Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue

“…Out of these cases, 10 showed expression of basal/myoepithelial markers (ie, Ck5/6, Ck14, Ck17 and EGFR). 19,21,26,27,30,31 Although NGFR showed no prognostic significance in this cohort, when its expression was analysed in a cohort of 37 basal-like breast carcinomas, 26 NGFR showed a statistically significant association with lack of lymph node metastasis. In addition, initial analysis in 37 basal-like breast carcinomas has revealed statistically significant associations between NGFR expression and longer disease-free and overall survival.…”

“…For tissue microarray and whole tissue section immunohistochemical analysis, a cutoff of 10% unequivocally stained neoplastic cells was adopted for ER, PR, basal markers and EGFR, 30 whereas HER2 was scored according to the Herceptest scoring system. 38 For basal markers, only cytoplasmic staining was considered specific, for EGFR and HER2 only membranous staining was regarded as specific and for ER and PR, only nuclear staining was considered specific.…”

“…There are several lines of evidence to suggest that highgrade breast carcinomas expressing basal/myoepithelial markers have distinct pathological features, expression profiles and, most importantly, clinical behaviour when compared to high-grade breast carcinomas devoid of basal-like differentiation. [23][24][25][26][27][28][29][30] The landmark studies of Perou et al 23 and Sorlie et al 24,25 revealed basal-like breast carcinomas to be more aggressive than oestrogen receptor (ER)-positive cancers, the former having significantly shorter disease-free and overall survival. Furthermore, recent data from our laboratory have suggested that basal tumours are heterogenous in terms of their molecular genetic profiles and that there might be a subgroup with a more favourable prognosis.…”