Neuroendocrine differentiation correlates with hormone receptor expression and decreased survival in patients with invasive breast carcinoma

Kwon, Sun Young; Bae, Young Kyung; Gu, Mi Jin; Choi, Jung Eun; Kang, Su Hwan; Lee, Soo Jung; Kim, Aeri; Jung, Hye Ra; Kang, Sanggil; Oh, Hoon Kyu; Park, Ji Young

doi:10.1111/his.12306

Cited by 53 publications

(73 citation statements)

References 19 publications

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“…Cumulating evidence demonstrates that Schwann-like cell differentiation may be one of the likely PNI molecular mechanisms in neurotropic cancers (12,13,(28)(29)(30). Reed and Leonard firstly reported that the specific differentiation toward 'neuroma-like' qualities in melanoma may be relative to the PNI characteristics of melanoma cells (31).…”

Section: Discussionmentioning

confidence: 99%

Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis

et al. 2015

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Abstract. Perineural invasion (PNI) is a striking biological behavior observed in salivary adenoid cystic carcinoma (SACC). The present study was designed to establish a co-culture model of SACC cells with Schwann cells (SCs), and then study epithelial-mesenchymal transition (EMT) and the Schwann-like differentiation of SACC cells to investigate the likely molecular mechanism of PNI. The co-culture models of SCs with tumor cells (SACC-83, SACC-LM and MEC-1) were established using a Transwell system. An elevated concentration of brain-derived neurotrophic factor (BDNF) was detected by ELISA assay in the co-cultured medium of the SACC-83 group and SACC-LM group rather than the MEC-1 group. The EMT process and Schwann-like differentiation in SACC-83 cells were analyzed by RT-PCR, western blotting, immunofluorescence, photography, and migration and perineural invasion assays. The SACC-83 cells under the co-culture condition with SCs changed to a mesenchymal morphology and had higher migration and invasion capabilities compared with the solely cultured SACC-83 cells, accompanied by the downregulation of E-cadherin and upregulation of N-cadherin and vimentin. The co-cultured SACC-83 cells also developed Schwann-like differentiation with increased expression of SC markers, S100A4 and GFAP. However, inhibition of tropomyosin-related kinase B (TrkB) by K252a markedly blocked these effects. Additionally, the expression and correlation of TrkB, E-cadherin and S100A4 were analyzed by immunohistochemistry in 187 primary SACC cases. The levels of TrkB and S100A4 expression were both positively associated with PNI in the SACC cases, while E-cadherin expression was negatively associated with PNI. Elevated expression of TrkB was significantly correlated with the downregulated expression of E-cadherin and the upregulated expression of S100A4 in the SACC cases. Our results suggest that SCs play a pivotal role in the PNI process by inducing the EMT process and the Schwann-like differentiation of SACC cells via the BDNF/TrkB axis. Interruption of the interreaction between SACC cells and SCs by targeting the BDNF/TrkB axis may be a potential strategy for anti-PNI therapy in SACC.

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Section: Discussionmentioning

confidence: 99%

Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis

et al. 2015

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“…The prognostic relevance of neuroendocrine differentiation in breast carcinoma is still debated because several studies have been published with mixed results [3,6,[31][32][33][34][35]. These conflicting results might be explained by the limited number of cases reported in each series, by the different inclusion criteria based on whether the 2003 or 2012 WHO definitions were applied to identify NECB, and also by the analysis performed considering NECB as a whole, without analyzing the outcomes according to the different histologic subtypes.…”

Section: Prognosismentioning

confidence: 99%

Neuroendocrine Carcinoma of the Breast: Current Evidence and Future Perspectives

et al. 2015

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Neuroendocrine carcinoma of the breast is considered a rare entity, and for this reason there are no data from prospective clinical trials on its optimal management. Early stage tumors are usually treated with the same strategy used for the other types of invasive breast cancer. Anthracycline-and taxane-based regimens represent the most frequently administered chemotherapy in neoadjuvant and adjuvant setting, as well as for metastatic disease, although combinations of platinum compounds and etoposide have been widely used, in particular for small-cell histology and tumors with a high proliferation index. For metastatic disease, a multimodality therapeutic strategy can be considered on an individual basis, with chemotherapy, endocrine therapy, peptide receptor radionuclide therapy, radiation therapy, surgery, or a combination of the above. In the near future, a better knowledge of the biology of these tumors will hopefully provide new therapeutic targets for personalized treatment. In this review, we discuss the current evidence and the future perspectives on diagnosis and treatment of neuroendocrine carcinoma of the breast. The Oncologist 2016;21:28-32 Implications for Practice: Neuroendocrine carcinoma of the breast (NECB) is a distinct entity of breast cancer. Clinical features and morphology are not helpful to distinguish NECB from other subtypes of breast cancer; therefore, immunohistochemistry markers for neuroendocrine differentiation, mainly chromogranin and synaptophysin, should be routinely used to confirm the diagnosis, especially in cases of mucinous or solid papillary carcinoma in which the suspicion of NECB may be relevant. Adjuvant treatment should be offered according to the same recommendations given for the other types of invasive breast cancer. An accurate diagnosis of NECB is also important in the metastatic setting, in which a multimodality approach including specific therapies such as peptide receptor radionuclide therapy can be considered.

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“…Among all invasive breast cancers, neuroendocrine differentiation has been reported in 4–30% of cases, on the basis of immunohistochemistry. The wide range in the reported frequency of neuroendocrine differentiation is probably related to a variety of factors, including the particular markers studied and the threshold used for marker positivity.…”

Section: Carcinomas With Neuroendocrine Differentiationmentioning

confidence: 99%

Papillary and neuroendocrine breast lesions: the WHO stance

et al. 2015

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In this review, we highlight adaptations in the WHO 2012 classification of papillary and neuroendocrine breast lesions as compared with the previous 2003 version. Consensus criteria for distinguishing atypical ductal hyperplasia from ductal carcinoma in situ within an intraductal papilloma are proposed. The absence of myoepithelial cells around the wall of an encapsulated papillary carcinoma, although raising consideration of an indolent tumour with minimal invasion, is currently regarded as in-situ disease for staging purposes. The majority of solid papillary carcinomas are classified as in-situ tumours, but lesions with irregular tumour islands within desmoplastic stroma may be considered to be invasive. The diagnosis of solid papillary carcinoma without further qualification as either in-situ or invasive disease is discouraged. When invasive papillary carcinoma is seen in the breast, metastatic papillary carcinoma from other organ sites needs to be excluded. WHO 2012 classifies neuroendocrine breast tumours as well-differentiated neuroendocrine tumour, small-cell carcinoma, and invasive breast carcinoma with neuroendocrine differentiation. There is currently no clinical impact of identifying neuroendocrine differentiation in conventional invasive breast carcinomas, apart from acknowledging its frequent occurrence in subtypes such as the hypercellular variant of mucinous carcinoma and solid papillary carcinoma.

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Neuroendocrine differentiation correlates with hormone receptor expression and decreased survival in patients with invasive breast carcinoma

Abstract: IBC with NE differentiation is a distinct subtype of mammary carcinoma with an aggressive clinical outcome.

Cited by 53 publications

References 19 publications

Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis

Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis

Neuroendocrine Carcinoma of the Breast: Current Evidence and Future Perspectives

Papillary and neuroendocrine breast lesions: the WHO stance

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