Clinical implications for nestin protein expression in breast cancer

Abstract

Recently, it was observed that nestin is preferentially expressed in basal ⁄ myoepithelial cells of the mammary gland, and that this intermediate filament may be used as a myoepithelial marker. However, the clinical and prognostic implications of nestin as a marker for breast cancer are still unclear. We examined mastectomy specimens from 150 breast cancers and matching, adjacent non-cancerous tissues using immunohistochemistry and western blotting. Overall, triple-negative breast cancers -that is, breast cancers that do not express estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptor 2 (HER2 ⁄ neu) -had higher expression rates for nestin than the other breast cancers (57.14% vs 9.30%; P < 0.001). In triple-negative breast cancers, significantly increased nestin expression rates were observed in patients with lymph node metastasis compared with those without node metastasis (25.00% vs 76.92%; P = 0.032). A similar phenomenon was observed for invasive ductal carcinomas compared with ductal carcinoma in situ (16.67% vs 73.33%; P = 0.046). Nestin expression was also found to be significantly related to ER, PR, and P53 expression (P < 0.05). Nestin expression was associated with both shorter breast cancer-specific survival and poor relapse-free survival in the lymph node-positive group (P = 0.028 and P = 0.012 respectively). After Cox regression was carried out, nestin was not shown to be an independent prognostic factor for breast cancer. These findings substantiate the possibility of using nestin as a marker for triple-negative breast cancer. Triple-negative breast cancer progression is associated with nestin; however, the underlying mechanisms of this relationship require further investigation. (Cancer Sci 2010; 101: 815-819) B reast carcinoma is the most common malignancy in women and is the second leading cause of cancer death in women.(1) Over the last 30 years, deaths from breast cancer have approximately tripled in Japan, which historically has had a low incidence of breast cancer.(2) According to the World Health Organization, more than 1.2 million people will be diagnosed with breast cancer each year worldwide.Breast cancer is a heterogeneous disease embracing several different phenotypes with consistently different biological characteristics.(3) Hormonal therapies (tamoxifen, anti-estrogens) and adjuvant chemotherapy (trastuzumab [Herceptin]) have benefited millions of patients with breast cancer.(4,5) Their success, however, is limited to a subset of patients whose tumors express estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2 ⁄ neu), tumor protein 53 (P53), and so on.(6) Therefore, the status of these proteins has prognostic ramifications for breast cancer.Nestin, a primeval protein marker for neural stem cells, is also expressed in follicle stem cells and their immediate, differentiated progeny.(7) It has recently received attention as a marker for newly formed endothelial cells. In their study, Teranishi...

Clinical significance of nestin and its association with survival in neuroendocrine lung tumours

“…As mentioned before, LCNEC is much more aggressive than carcinoids. Nestin is usually detected in more advanced tumour stages and in very malignant neoplasms [27,28]. Thus, presence of this protein in LC-NEC might be associated with properties of nestin positive cells: high plasticity and increased proliferative potential.…”

Prognostic impact of nestin expression in resected large cell neuroendocrine carcinoma of the lung

“…Although little is known about the biological function of nestin, some studies indicated that nestin may play an important role in the distribution and organization of critical cellular factors involved in regulating cell proliferation, survival, and differentiation [15,16]. Moreover, recent studies have shown that nestin is also expressed in epithelial tumors, such as pancreatic cancer [17], prostate cancer [18], and breast cancer [19], and its expression is associated with tumor aggressiveness. Recently, we reported that nestin is expressed in a subset of NSCLC and its expression is related to clinicopathological factors, and nestin expression is a prognostic indicator of poor survival among patients with resected NSCLC [20].…”

Stromal Signatures of Breast Carcinogenesis in Fibroadenoma—A Pilot Study

“…Nestin expression in breast cancer is correlated with increased rate of nodal metastasis and poor prognosis [24]. As such, overexpression of nestin has been suggested to be restricted to a very poorly-differentiated and highly aggressive tumour-type [23].…”

“…Normally, nestin acts as a scaffold to maintain cell shape and tissue stability and was originally reported only in neuroepithelial stem cells; however, expression has since been described in gastrointestinal tract, pancreas, salivary gland, kidney, uterine cervix, endometrium, prostate, and breast [22]. Within the breast, nestin is expressed in the basal and myoepithelial layer of the mammary gland where it is can be used as a marker for the formation of endothelial or myoepithelial cells [20,23,24]. In addition, this protein has been found to be active in newly formed blood vessels [21].…”

“…Overexpression of nestin is most common in basal-like breast cancers, often in the triple-negative tumours (negative for estrogenreceptors, progestin-receptors or HER2) [20,24]. Nestin expression in breast cancer is correlated with increased rate of nodal metastasis and poor prognosis [24].…”