The activated leukocyte cell adhesion molecule (ALCAM) is overexpressed in many mammary tumors, but controversial results about its role and prognostic impact in breast cancer have been reported. Therefore, we evaluated the biologic effects of ALCAM expression in two breast cancer cell lines and a larger cohort of mammary carcinomas. By stable transfections, MCF7 cells with ALCAM overexpression and MDA-MB231 cells with reduced ALCAM levels were generated and analyzed in functional assays and cDNA microarrays. In addition, an immunohistochemical study on 347 patients with breast cancer with long-term follow-up and analysis of disseminated tumor cells (DTCs) was performed. In both cell lines, high ALCAM expression was associated with reduced cell motility. In addition, ALCAM silencing in MDA-MB231 cells resulted in lower invasive potential, whereas high ALCAM expression was associated with increased apoptosis in both cell lines. Among genes which were differentially expressed in clones with altered ALCAM expression, there was an overlap of 15 genes between both cell lines, among them cathepsin D, keratin 7, gelsolin, and ets2 whose deregulation was validated by western blot analysis. In MDA-MB231 cells, we observed a correlation with VEGF expression which was validated by enzyme-linked immuno sorbent assay (ELISA). Our IHC results on primary breast carcinomas showed that ALCAM expression was associated with an estrogen receptor-positive phenotype. In addition, strong ALCAM immunostaining correlated with nodal involvement and the presence of tumor cells in bone marrow. By Kaplan-Meier analysis, strong ALCAM expression in ductal carcinomas correlated with shorter recurrence-free intervals (P=0.048) and overall survival (OAS, P=0.003). Our results indicate that the biologic role of ALCAM in breast cancer is complex, but overexpression might be relevant for outcome in ductal carcinomas.

Introduction: Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) gained increasing attention regarding tumorprogression and metastatic spread in breast cancer. The aim of this study was to examine ALCAM expression levels in primary breast cancer and distant metastases of the same patient within 29 autopsy cases to better understand the underlying mechanisms of metastases and the role of adhesion molecules in this process. Material and Methods: Paraffin-embedded tissue of the primary and distant metastases (N = 84) were collected and ALCAM immunohistochemistry was performed. Results: The primary tumor and all metastases showed a statistically normally distributed ALCAM expression. ALCAM expression level average differs between immunoreactive score (IRS) (mean) 4.16 (lung)-5.00 (adrenal gland). Of the metastatic ALCAM expression levels we obtained an intra-class correlation (ICC) of 80.9%, indicating a strong cluster effect of measurements in the same patient. ALCAM expression scores in metastatic sites and in the primary analyzed by hierarchical regression analysis showed that ALCAM expression in the primary is prognostic for ALCAM expression in all different sites of metastases (slope = 0.773, p < 0.001, r2 = 0.504). Conclusion: ALCAM expression in the primary is positively correlated to ALCAM expression in metastases within one single patient. This could show a tumorbiological context of ALCAM for the development of metastases in breast cancer.

Compared with CEACAM6, ALCAM showed significantly stronger protein expression in breast cancer skin metastases compared with metastases in all other sites.

In this paper, the potential of directional ultrasonic wave superposition by moving sound generators for laser beam welding of high-strength steel alloys 1.5528 (22MnB5) is studied. Steel sheets of identical thickness and in form of tailored blanks were joined in butt joint configuration. The influences of the various excitation parameters of the moving sound generators on the ultrasonic coupling and their influence on the distribution of the AlSi coating components within the melting zone and the weld seam characteristics are investigated. Etched cross-sections, scanning electron microscopy, energy dispersive X-ray spectroscopy, and electron backscattering measurements were used as the investigation methods to determine the AlSi distribution in the weld as well as its microstructure. The results presented a series of experiments which show that a suitable superposition of ultrasonic waves by the moving sound generators lead to a more homogeneous distribution of AlSi particles in the melt as well as to a finer microstructure within the weld, which improves the mechanical–technological properties.