Summary Breast cancer is a heterogeneous disease. Tumor cells and associated healthy cells form ecosystems that determine disease progression and response to therapy. To characterize features of breast cancer ecosystems and their associations with clinical data, we analyzed 144 human breast tumor and 50 non-tumor tissue samples using mass cytometry. The expression of 73 proteins in 26 million cells was evaluated using tumor and immune cell-centric antibody panels. Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. High frequencies of PD-L1 + tumor-associated macrophages and exhausted T cells were found in high-grade ER + and ER − tumors. This large-scale, single-cell atlas deepens our understanding of breast tumor ecosystems and suggests that ecosystem-based patient classification will facilitate identification of individuals for precision medicine approaches targeting the tumor and its immunoenvironment.

The present study was undertaken in order to elucidate the question of whether the distribution of stromal CD34+ fibrocytes and smooth muscle actin (SMA)-reactive myofibroblasts differs between benign and malignant lesions of the breast. We investigated a total of 31 ductal carcinomas and 27 specimens with benign lesions of the breast (ductal hyperplasia, sclerosing adenosis, fibroadenoma, phyllodes tumor) and compared the distribution of CD34+ fibrocytes and SMA-reactive myofibroblasts. The stroma of normal breast tissue contained CD34+ fibrocytes, whereas SMA-reactive myofibroblasts were absent. All benign breast lesions exhibited stromal CD34+ fibrocytes and few lesions (fibroadenomas and phyllodes tumor) showed additional SMA-reactive myofibroblasts. In invasive breast cancer the stroma was devoid of CD34+ fibrocytes but a varying number of stromal SMA-reactive myofibroblasts was detectable. In the setting of the present study the loss of CD34+ fibrocytes was specific for invasive breast cancer and ductal carcinoma in situ, whereas SMA-reactive myofibroblasts were observed in different benign and malignant lesions. These findings may be helpful tools in distinguishing benign breast lesions (e.g., sclerosing adenosis) from invasive breast cancer and in characterizing stromal remodeling associated with invasive cancer.

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We investigated tumor-free mucosa and squamous cell carcinomas of the oral cavity, the pharynx, and larynx with respect to the presence of stromal CD34+ fibrocytes and alpha-smooth muscle antigen (SMA)-positive myofibroblasts. Additionally, stromal expression of CD117 was analyzed. A total of 39 squamous cell carcinomas were assessed immunohistochemically. In all cases investigated, CD34+ fibrocytes were found in the tumor-free stroma, whereas alpha-SMA-positive myofibroblasts were lacking. Areas of lymphocytic infiltration disclosed a focal reduction of CD34+ fibrocytes. CD117 expression was absent from the tumor-free stroma. Of 39 squamous cell carcinomas, 33 were free of stromal CD34+ fibrocytes, and, in 31 carcinomas, stromal alpha-SMA-positive myofibroblasts occurred at least focally. CD117-positive stromal spindle cells were found in 25 carcinomas. Compared with tumor-free mucosa, the number of tissue mast cells was significantly increased in carcinomas. We conclude that stromal remodeling induced by invasive carcinomas is characterized by a loss of CD34+ fibrocytes and subsequent gain of alpha-SMA-positive myofibroblasts. The diagnostic impact of this finding is, however, limited by the fact that chronic inflammation may also be accompanied by a focal loss of CD34+ fibrocytes.

The number of regional lymph nodes was determined in sites relevant to lymphadenectomy in gastric cancer in 30 cadavers. Tissue was cleared by dissolving fatty tissue, thus making lymph nodes with a diameter of at least 1 mm visible. All lymph node stations indicated by the Japanese Research Society for Gastric Cancer were studied. In stations 1-11 (corresponding with R2 resection) an average of 27 nodes (range 17-44 nodes) was found, whereas stations 1-16 (corresponding with R3 resection) showed an average of 43 nodes (range 25-64 nodes). These values are higher than those usually obtained from lymphadenectomy for gastric cancer. Striking individual differences in the total number of lymph nodes and the number of single stations was observed. The number of lymph nodes in these investigations are the normal anatomical values and serve as quality control of lymph node dissection in gastric carcinoma.

Objectives: Adrenocortical carcinoma (ACC) is a rare malignant neoplasm with extremely poor prognosis. The molecular mechanisms of adrenocortical tumorigenesis are still not well understood. The comparative analysis by cDNA microarrays of gene-expression patterns of benign and malignant adrenocortical tumors allows us to identify new tumor-suppressor genes and proto-oncogenes underlying adrenocortical tumorigenesis. Design and methods: Total RNA from fresh-frozen tissue of 10 ACC and 10 benign adrenocortical adenomas was isolated after histologic confirmation of neoplastic cellularity of at least 85%. The reference consisted of pooled RNA of 10 normal adrenal cortex samples. Amplified RNA of tumor and reference was used to synthesize Cy3-and Cy5-fluorescently labeled cDNA in a flip-color technique. D-chips containing 11 540 DNA spots were hybridized and scanned and the images were analyzed by ImaGene 3.0 software. Results: The comparative analysis of gene expression revealed many genes with more than fourfold expression difference between ACC and normal tissue (42 genes), cortical adenoma and normal tissue (11 genes), and ACC and cortical adenoma (21 genes) respectively. As confirmed by realtime PCR, the IGF2 gene was significantly upregulated in ACCs versus cortical adenomas and normal cortical tissue. Genes that were downregulated in adrenocortical tumors included chromogranin B and early growth response factor 1. Conclusions: Comprehensive expression profiling of adrenocortical tumors by the cDNA microarray technique is a very powerful tool to elucidate the molecular steps associated with the tumorigenesis of these ill-defined neoplasms. To evaluate the role of identified genes, further detailed analyses, including correlation with clinical data, are required.European Journal of Endocrinology 154 587-598

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It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50 years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.