Tumor vascularization and clinicopathologic parameters as prognostic factors in merkel cell carcinoma

Боб, А. О.; Nielen, F.; Krediet, Jorien Tannette; Schmitter, Julia; Freundt, D.; Terhorst‐Molawi, Dorothea; Röwert‐Huber, Joachim; Kanitakis, Jean; Stockfleth, Eggert; Ulrich, Ch.; Weichenthal, Michael; Egberts, Friederike; Lange‐Asschenfeldt, Bernhard

doi:10.1007/s00432-017-2455-x

Cited by 9 publications

(5 citation statements)

References 41 publications

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“…We found a clear association of DAGs with angiogenesis. Angiogenesis plays a crucial role in the progression of solid tumors, and increased tumor vascularization is a factor predicting poor prognosis in MCC [ 22 ]. VEGFA, a proangiogenic growth factor that was among the DAGs, has been found to be expressed in the majority of MCC tumors based on immunohistochemistry results.…”

Section: Discussionmentioning

confidence: 99%

Activation of Oncogenic and Immune-Response Pathways Is Linked to Disease-Specific Survival in Merkel Cell Carcinoma

Sundqvist

Kilpinen

Böhling

et al. 2022

Cancers

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Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin with a poor prognosis. Improving the prognosis of MCC by means of targeted therapies requires further understanding of the mechanisms that drive tumor progression. In this study, we aimed to identify the genes, processes, and pathways that play the most crucial roles in determining MCC outcomes. Methods: We investigated transcriptomes generated by RNA sequencing of formalin-fixed paraffin-embedded tissue samples of 102 MCC patients and identified the genes that were upregulated among survivors and in patients who died from MCC. We subsequently cross-referenced these genes with online databases to investigate the functions and pathways they represent. We further investigated differential gene expression based on viral status in patients who died from MCC. Results: We found several novel genes associated with MCC-specific survival. Genes upregulated in patients who died from MCC were most notably associated with angiogenesis and the PI3K-Akt and MAPK pathways; their expression predominantly had no association with viral status in patients who died from MCC. Genes upregulated among survivors were largely associated with antigen presentation and immune response. Conclusion: This outcome-based discrepancy in gene expression suggests that these pathways and processes likely play crucial roles in determining MCC outcomes.

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Section: Discussionmentioning

confidence: 99%

Activation of Oncogenic and Immune-Response Pathways Is Linked to Disease-Specific Survival in Merkel Cell Carcinoma

Sundqvist

Kilpinen

Böhling

et al. 2022

Cancers

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“…These results gave an initial indication of the molecular mechanism responsible for the high vascular density observed in certain MCC cases that was associated with lower progression-free survival (PFS) [91] and overall survival (OS) [92].…”

Section: Angiogenesismentioning

confidence: 96%

Merkel Cell Carcinoma

et al. 2021

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Merkel cell carcinoma (MCC) is a rare and extremely aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. This review intends to propose a comprehensive evaluation of MCC epidemiology, clinical features, pathogenetic mechanisms, diagnosis, and therapies. A section is dedicated to immunological aspects and another to the involvement of angiogenesis and angiogenic growth factors in MCC progression, proposing novel diagnostic and therapeutic approaches. Advanced MCC tumors have been treated with immune checkpoint inhibitors with effective results. Therefore, the state of art of this immunotherapy is also examined, reporting on the most recent clinical trials in the field. We conclude by underlining the achievements in the understanding of MCC pathology and indicating the present needs for effective diagnosis and therapeutic management of the disease.

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“…Consistent with these proposal, we observed a significant increase in vascular density in tumors with highest colocalized B7-H3/CD31 expression, and this was particularly true in primary MCCs with a more aggressive pattern of growth (infiltrative). Prior studies on primary MCC have correlated an increased vascular density with reduced progression-free survival (56) and disease-specific survival (57). Together with the lack of correlation between colocalized expression of B7-H3 and CD31 with the composition or density of the tumor-associated immune infiltrate (an additional mechanism to delimit tumor growth), these findings argue that B7-H3 expression in the endothelial cells of primary MCC may drive vascular proliferation through activation of proangiogenic pathways.…”

Section: B7-h3 Expression Inmentioning

confidence: 86%

B7-H3 Expression in Merkel Cell Carcinoma–Associated Endothelial Cells Correlates with Locally Aggressive Primary Tumor Features and Increased Vascular Density

Aung

Parra

Barua

et al. 2019

Clinical Cancer Research

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Tumor vascularization and clinicopathologic parameters as prognostic factors in merkel cell carcinoma

Cited by 9 publications

References 41 publications

Activation of Oncogenic and Immune-Response Pathways Is Linked to Disease-Specific Survival in Merkel Cell Carcinoma

Activation of Oncogenic and Immune-Response Pathways Is Linked to Disease-Specific Survival in Merkel Cell Carcinoma

Merkel Cell Carcinoma

B7-H3 Expression in Merkel Cell Carcinoma–Associated Endothelial Cells Correlates with Locally Aggressive Primary Tumor Features and Increased Vascular Density

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