Distinct expression of cytokeratin, N-cadherin and CD133 in circulating tumor cells of metastatic breast cancer patients.

AIM: Circulating tumor cells (CTCs) appear as potential candidates to predict the ability of breast tumors to metastasize. Moreover, epithelial-mesenchymal transition (EMT) and stem cell features are major mechanisms for metastasis. PATIENTS & METHODS: Using a triple fluorescence technique, the expression of EMT (N-cadherin) and stem cell markers (CD133) was analyzed in CTCs detected via cytokeratin in blood samples from 26 metastatic breast cancer patients. RESULTS: We detected CTCs in 100% of the patients (n = 831 CTCs). In total, 67% of the CTCs were N-cadherin and CD133 negative. Nonetheless, 87.8 and 57.6%, respectively, of the CTCs that expressed one marker coexpressed the other. Both double-negative and double-positive CTCs were present in more than 90% of the patients. Within the CTCs of each patient, we demonstrated striking heterogeneities of marker expressions, cell shapes, clusters and sizes. CONCLUSION: These data outline the importance of characterizing CTCs, especially through stem cell and EMT markers.

A Friend in Need Is a Friend Indeed? Analysis of the Willingness to Share Self-Produced Electricity During a Long-lasting Power Outage.

Will private households owning a photovoltaic system share their electricity during a long-lasting power outage? Prior research has shown that our energy systems need to become more resilient by using dispersed energy sources-a role that could well be performed by these private photovoltaic systems, but only if their owners decide to share the produced electricity, and not consume it themselves. Considering the potential of this approach, it is indispensable to better understand incentives and motives that facilitate such cooperative behaviour. Drawing on theories of social dilemmas as well as prosocial behaviour, we hypothesize that both, structural solutions such as increased rewards as well as individual motives such as empathy-elicited altruism and norms predict cooperation. We test these hypotheses against a dataset of 80 households in Germany which were asked about their sharing behaviour towards four different recipient groups. We show that the effectiveness of motives differs significantly across recipient groups: Individual (intrinsic) motivations such as empathy-elicited altruism and altruistic norms serve as a strong predictor for cooperative behaviour towards related recipients as well as critical infrastructure, whereas higher rewards partially even reduce cooperation depending on the donor's social value orientation. For the recipient groups neighbours and public infrastructure, no significant effect for any of the tested incentives is found. Contributing to literature on social dilemmas and energy resilience, these results demonstrate the relevance of individual rather than structural incentives for electricity sharing during a power outage to render our energy provision more resilient. Practical implications for policymakers are given.

Estrogen Receptor and HER2 Status on Disseminated Tumor Cells and Primary Tumor in Patients with Early Breast Cancer.

BACKGROUND: We evaluated both estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status on disseminated tumor cells (DTCs) in the bone marrow of 54 patients with early breast cancer and compared these with the corresponding primary tumor (PT). MATERIALS AND METHODS: Bone marrow aspirates were obtained at the time of first surgery, and ER and HER2 status on DTCs was assessed simultaneously by immunocytochemistry using a triple fluorescence staining method. RESULTS: The median number of DTCs was 13 (range 1-95). The concordance rate between ER status on DTC and PT was 74%. Patients with an ER-positive PT were significantly more likely to have at least one ER-positive DTC (34 out of 42) than patients with an ER-negative PT (6 out of 12; P = .031). Thirty-nine (93%) of the 42 patients with ER-positive PT had at least one ER-negative DTC. The concordance rate between HER2 status on DTC and PT was 52%. The probability of having at least one HER2-positive DTC was not related to the HER2 status of the PT (P = 0.56). Twenty-two (46%) of the 48 patients with a HER2-negative PT had at least one HER2-positive DTC. All the six patients with a HER2-positive PT had at least one HER2-negative DTC. CONCLUSION: Taken together, our study confirms that ER and/or HER2 status may differ between DTC and PT. This discordance could be important for patients lacking ER or HER2 expression on the PT but showing ER-positive or HER2-positive DTC because they might benefit from an endocrine and/or HER2-targeted therapy.

Strong correlation between N-cadherin and CD133 in breast cancer: role of both markers in metastatic events.

PURPOSE: Epithelial mesenchymal transition is a major mechanism to explain metastatic events in breast cancer. Another important aspect is that cells with stem cell properties are able to become resistant against chemotherapeutics. Our main goal was to investigate the role of the EMT marker, N-cadherin, and of the stem cell marker, CD133, in breast cancer. METHODS: The expressions of N-cadherin and CD133 were assessed by immunohistochemistry in 307 primary tumors from breast cancer patients and for 30 patients, in the related recurrences and/or metastases. We studied the correlation between both markers, their associations with known clinicopathological parameters and their role as predictive markers for survival time. Different expressions of both markers in primary tumor and recurrences or metastases were examined. RESULTS: N-cadherin and CD133 expressions correlated positively in the 261 primary tumor samples (p = 0.000) and in the 45 primary tumor, recurrence or metastasis samples (p = 0.010). In patients without lymph node metastases, the 10-year survival time was significantly lower when the tumor was N-cadherin-positive (p = 0.042). Expression of N-cadherin was also significantly higher in metastases than in the related primary tumors (p = 0.039). CONCLUSION: N-cadherin and CD133 expressions are strongly correlated and N-cadherin appears as a potential metastases marker in a specific patient subpopulation.

Hormone receptor status, erbB2 expression and cancer stem cell characteristics of circulating tumor cells in breast cancer patients.

The most important predictor for disease-free and overall survival of breast cancer patients is the presence of axillary lymph node metastasis. For surveillance during recurrence-free follow-up or in metastatic disease no marker is available at the moment. Several trials have shown the prognostic relevance of circulating tumor cells (CTC) in early and metastatic breast cancers. Indeed, only CTC that exhibit specific molecular characteristics including stem cell characteristics, could be able to create new metastasis. Hormone therapy or anti-erbB2 therapies are prescribed according to the hormone (ERα/PR expression) and erbB2 status of the initial tumor. Nonetheless, it appears that the CTC, and consequently the metastatic cells, may have a very different hormone and erbB2 status. An optimal individualized treatment could then be obtained by characterizing ERα and erbB2 status in the CTC and comparing it to the primary tumor.

Heterogeneity of ERα and ErbB2 Status in Cell Lines and Circulating Tumor Cells of Metastatic Breast Cancer Patients.

Hormone therapy and anti-ErbB2 therapies are prescribed according to the hormone receptor [estrogen receptor α (ERα)/progesterone receptor] and ErbB2 status of the initial tumor, but it appears that circulating tumor cells (CTCs) and, consequently, the metastatic cells may have a different receptor status. As an attempt to meet the crucial need for identification of the subpopulation of patients that will benefit from more individualized therapies, rapidly evolving therapies should allow a profiling of the tumors and/or of the CTCs. We established a triple fluorescence staining using eight cell lines to visualize the CTCs (cytokeratin detection) and then to define their individual ERα and ErbB2 status. Afterward, we used this method for blood samples from 26 metastatic breast cancer patients. We identified major differences of ERα levels between the cell lines and even within one cell line. For the metastatic patients, we detected and characterized CTCs in 38.5% of the patients with a total of 92 CTCs. We could demonstrate that at least 69.6% of the CTCs exhibit an ERα and/or ErbB2 status different from the status of the primary tumor and that the CTCs from only 30% of the patients had no change of receptor status. Strikingly, heterogeneities of the status, aggregation, and size clearly appear within the CTCs. The data we generated outline the importance of a profiling not only of tumors but also of CTCs to establish individualized treatments. CTCs may then appear as new prognosis and treatment marker for both metastatic and adjuvant breast cancers.