Abstract

Definitions of basal-like breast cancer phenotype vary, and microarray-based expression profiling analysis remains the gold standard for the identification of these tumors. Immunohistochemical identification of basal-like carcinomas is hindered with a fact, that on microarray level not all of them express basal-type cytokeratin 5/6, 14 and 17. We compared expression of cytokeratin 5, 14 and 17 in 115 patients with operable breast cancer estimated by real-time RT-PCR and immunohistochemistry.Despite the method of dichotomization and statistical analysis, there were cases with discordant results comparing immunohistochemistry and RT-PCR analysis. For dichotomisation based on quartiles and ROC, 14% of cases were negative on immunohistochemical examination for CK5/6, but presented high CK5 mRNA levels. There were also 48-55% cases, which were CK5/6-immunopositive, but were negative by mRNA examination. Similar discordances were observed for CK14 and CK17.Basal keratin mRNAs did not correlate with ER mRNA levels, while immunohistochemistry produced significant relationship with ER status.Our observation suggest that both method may produce different results in a small proportion of cases. Discordance between immunohistochemistry and RT-PCR may confound attempts to establish a simple methods for identification of basal-like tumors.

Highlights

  • Heterogeneity of breast cancer at the molecular level was supported by data from cDNA microarrays [1,2]

  • Basal-like subtype is characterized by multigenetic signature, usually with high expression of high molecular weight cytokeratins normally expressed in basal myoepithelial cells: keratin 5 (CK5), 14 (CK14) and keratin 17 (CK17) [1,2]

  • In 73 cases (63,5%) identified immunohistochemically as being CK5/6-negative, mean CK5 gene expression was significantly lower, than in cases classified by immunostaining as being CK5/6-positive

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Summary

Introduction

Heterogeneity of breast cancer at the molecular level was supported by data from cDNA microarrays [1,2]. Basal-like subtype is characterized by multigenetic signature, usually with high expression of high molecular weight cytokeratins normally expressed in basal myoepithelial cells: keratin 5 (CK5), 14 (CK14) and keratin 17 (CK17) [1,2]. They usually express vimentin and p-cadherin, and more than 60% of them express epidermal growth factor receptor (EGFR) [3,4]. A great interest in basal like-cancers produced attempts to determine basal-like tumors by the use of a much more easier technique such as immunohistochemistry.

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