Nestin expression associates with poor prognosis and triple negative phenotype in locally advanced (T4) breast cancer

Abstract

Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients' outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC) subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02) and with borderline significance at 10-years of survival (P=0.05) in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers.

Stem cell markers OCT4 and nestin in laryngeal squamous cell carcinoma and their relation to survivin expression

“…Although the precise function of nestin remains to be elucidated, studies suggest that it may play a role in the control of cell proliferation, survival and differentiation [36]. Nestin is also a putative marker of CSCs [6,39], and recent studies have demonstrated that it is expressed in epithelial tumors, such as breast cancer [32], gastric cancer [6], and non-small cell lung cancer [39]. To the knowledge of the authors, the expression of nestin in LSCC has not been studied before.…”

Inflammatory Breast Cancer Stem Cells: Contributors to Aggressiveness, Metastatic Spread and Dormancy

“…SLUG up-regulation in turn promotes a stem cell phenotype within breast cancer cells [40]. Additional pathways implicated in the breast cancer stem cell phenotype include those of aldehyde dehydrogenase [41], bone morphogenic protein (BMP), Wnt [42] and ganglioside GD2 [43].…”

“…Tumor cells isolated from the MARY-X model of human IBC express both embryonal stem cell markers (Nestin, Rex1, and Stellar) and the classic breast cancer stem cell signature (CD44+/CD24-/CD133+/aldehyde dehydrogenase1 (ALDH1)+) [31]. Furthermore, 74% of human IBC samples contain a genetic signature indicative of a high cancer stem cell composition, as opposed to 44% of non-IBC samples [42]. Stem cell-related signaling, particularly through Hedgehog and transforming growth factor beta (TGFβ), is also more active in IBC vs. non-IBC samples [42].…”

“…Furthermore, 74% of human IBC samples contain a genetic signature indicative of a high cancer stem cell composition, as opposed to 44% of non-IBC samples [42]. Stem cell-related signaling, particularly through Hedgehog and transforming growth factor beta (TGFβ), is also more active in IBC vs. non-IBC samples [42]. Nestin, a protein primarily associated with neural stem cells, is highly expressed in both triple negative and IBC tumors [44].…”

Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer

“…Nestin has been shown to be expressed in newly formed blood vessels and tumour cells in various neoplasms, including glioblastoma, and prostate, pancreatic, lung, colorectal and breast cancer (1)(2)(3)(4)(5)(6). The expression of nestin indicates a poor prognosis in patients with colorectal cancer and prostate cancer, where nestin expression is found not in the cancer cells, but rather in the vascular endothelial cells, suggesting one or more significant roles of nestin in tumour neovascularization (2,5).…”