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  • 1
    In: International Journal of Cancer, Wiley, Vol. 150, No. 12 ( 2022-06-15), p. 2058-2071
    Abstract: Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread. Several recent single‐cell studies have provided detailed insights into the cellular heterogeneity of more common lung cancers, such as adeno‐ and squamous cell carcinoma. However, the characteristics of lung carcinoids on the single‐cell level are yet completely unknown. To study the cellular composition and single‐cell gene expression profiles in lung carcinoids, we applied single‐cell RNA sequencing to three lung carcinoid tumor samples and normal lung tissue. The single‐cell transcriptomes of carcinoid tumor cells reflected intertumoral heterogeneity associated with clinicopathological features, such as tumor necrosis and proliferation index. The immune microenvironment was specifically enriched in noninflammatory monocyte‐derived myeloid cells. Tumor‐associated endothelial cells were characterized by distinct gene expression profiles. A spectrum of vascular smooth muscle cells and pericytes predominated the stromal microenvironment. We found a small proportion of myofibroblasts exhibiting features reminiscent of cancer‐associated fibroblasts. Stromal and immune cells exhibited potential paracrine interactions which may shape the microenvironment via NOTCH, VEGF, TGFβ and JAK/STAT signaling. Moreover, single‐cell gene signatures of pericytes and myofibroblasts demonstrated prognostic value in bulk gene expression data. Here, we provide first comprehensive insights into the cellular composition and single‐cell gene expression profiles in lung carcinoids, demonstrating the noninflammatory and vessel‐rich nature of their tumor microenvironment, and outlining relevant intercellular interactions which could serve as future therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 218257-9
    detail.hit.zdb_id: 1474822-8
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  • 2
    In: Histopathology, Wiley, Vol. 75, No. 3 ( 2019-09), p. 431-436
    Abstract: In thymic carcinomas, focal clear cell change is a frequent finding. In addition to a prominent, diffuse clear cell morphology, some of these carcinomas show an exuberant hyalinised extracellular matrix, and therefore probably represent a separate entity. However, a characteristic genomic alteration remains elusive. We hypothesised that, analogous to hyalinising clear cell carcinomas of the salivary gland, hyalinising clear cell carcinomas of the thymus might also harbour EWSR1 translocations. Methods and results We identified nine archived cases of thymic carcinoma with focal clear cell features and two cases that showed remarkable hyalinised stroma and prominent, diffuse clear cell morphology. These two cases expressed p40 and were negative for Pax8, CD5, and CD117. Programmed death‐ligand 1 was highly positive in one case (70%), and negative in the other one. EWSR1 translocation was identified in both cases of hyalinising clear cell carcinoma, and was absent in all nine carcinomas that showed clear cell features without substantial hyalinisation. In one of the EWSR1 ‐translocated cases, a fusion between exon 13 and exon 6 of EWSR1 and ATF1 , respectively was identified by next‐generation sequencing. Conclusions These findings suggest that the EWSR1 translocation and possibly the EWSR1–ATF1 fusion might be unifying genomic alterations for thymic clear cell carcinomas with prominent hyalinised stroma, for which we propose the term ‘hyalinising clear cell carcinoma of the thymus’. Because the immunophenotype is unspecific, testing for the EWSR1 translocation might be helpful in discriminating this entity from other thymic neoplasms or metastases, in particular those with clear cell change.
    Type of Medium: Online Resource
    ISSN: 0309-0167 , 1365-2559
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2006447-0
    detail.hit.zdb_id: 131914-0
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