Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer.

Francesca Collina,Margherita Cerrone,Maurizio Di Bonito,Carlo Vitagliano,Francesco Nuzzo,Valeria Li Bergolis,Gerardo Botti,Michelino De Laurentiis,Monica Cantile

doi:10.1155/2015/158682

Francesca Collina, Margherita Cerrone + Show 7 more

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https://doi.org/10.1155/2015/158682

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Abstract

Triple-negative breast cancer (TNBC) has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as CD44, CD24, CD133, ALDH1, and ABCG2. The role of these markers in breast cancer is not clear yet and above all there are conflicting opinions about their real prognostic value. To investigate the role of CSCs markers in TNBC cancerogenesis and tumor progression, we selected 160 TNBCs samples on which we detected protein expression of CD44, CD24, CD133, ALDH1, and ABCG2 by immunohistochemistry. Our results highlighted a real prognostic role only for CD44 in TNBCs. All other CSCs markers do not appear to be related to the survival of TNBC patients. In conclusion, despite the fact that the presence of the cancer stem cells in the tumor provides important information on its potential aggressiveness, today their detection by immunohistochemistry is not sufficient to confirm their role in carcinogenesis, because specific markers probably are not yet identified.

Highlights

Triple-negative breast cancer (TNBC) (tumors that do not express estrogen receptor (ER) and progesterone receptor (PR) genes and with nonoverexpressed/nonamplified HER-2 gene) accounts for 10%–24% of invasive breast cancers, and it is typically high-grade tumor with different histological types
Metastatic lymph nodes were found in 43.1% (66/153) of patients at surgery, while distant metastases were found in 24.4% (39/155). 5 cases were unable to recover this information
Based on statistical elaboration of CD44 protein expression analysis with the other clinicopathological parameters in TNBC, considering only cytoplasmic expression, we showed that CD44 was significantly associated with metastases (p = 0.011) (Table 1) and with Disease-Free Survival (DFS) (p = 0.051) (Figure 2)

Summary

Introduction

Triple-negative breast cancer (TNBC) (tumors that do not express estrogen receptor (ER) and progesterone receptor (PR) genes and with nonoverexpressed/nonamplified HER-2 gene) accounts for 10%–24% of invasive breast cancers, and it is typically high-grade tumor with different histological types. Lehmann et al, by gene expression profiles studies, have further stratified the TNBCs into 6 subtypes, expressing many different molecular markers specific for the different groups [6] More recently, another RNA and DNA genomic profiles study showed that TNBCs can be divided into four fundamental subtypes with molecular characteristics even more specific, often targets of biological therapies, with differential potentiality of aggressiveness [7]. In both studies, the molecular more aggressive subtypes were those associated with the expression of immunomodulatory and stem-like molecules

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