Expression of Merkelcell polyomavirus (MCPyV) large T-antigen in Merkel cell carcinoma lymph node metastases predicts poor outcome

Haymerle, Georg; Janik, Stefan; Fochtmann, Alexandra; Pammer, Johannes; Schachner, Helga; Nemec, Lucas; Mildner, Michael; Houben, Roland; Grasl, Matthäus Ch.; Erovic, Boban M.

doi:10.1371/journal.pone.0180426

Cited by 11 publications

(10 citation statements)

References 21 publications

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“…This finding would indicate that patients with MCPyV positive tumour specimens suffer a higher rate of metastatic disease. In current literature, it was previously suggested that the MCPyV status correlates with patients’ prognosis . However, in contrast to our findings Sihto et al concluded that patients with MCPyV positive MCCs have a better survival than those with MCPyV negative tumours.…”

Section: Discussioncontrasting

confidence: 99%

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Expression of 15‐lipoxygenase‐1 in Merkel cell carcinoma is linked to advanced disease

Fochtmann-Frana

Haymerle

Schachner

et al. 2018

Clinical Otolaryngology

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Section: Discussioncontrasting

confidence: 99%

“…In current literature, it was previously suggested that the MCPyV status correlates with patients' prognosis. [49][50][51] However, in contrast to our findings Sihto et al 50…”

Section: Discussioncontrasting

confidence: 99%

Expression of 15‐lipoxygenase‐1 in Merkel cell carcinoma is linked to advanced disease

Fochtmann-Frana

Haymerle

Schachner

et al. 2018

Clinical Otolaryngology

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“…Additional biomarkers previously explored in MCC include: nuclear survivin expression [85]; activating mutations in PIK3CA, a key kinase in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) oncogenic pathway MCC [86]; expression of hedgehog pathway molecules [87,88], although hedgehog inhibitors have not shown efficacy against MCC [89]; and markers of cell cycle and cell proliferation [90,91]. In general, MCPyV + MCCs have been shown to have a better prognosis compared to MCPyV-MCCs [39,86,92,93]-both when primary and metastatic lesions are tested [94], although not all studies agree [95,96].…”

Section: Prognostic Biomarkers In Merkel Cell Carcinomasmentioning

confidence: 99%

Update on Merkel Cell Carcinoma

Tetzlaff

Nagarajan

2018

Head and Neck Pathol

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Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Incidence of MCC continues to rise, and risk factors include advanced age, pale skin, chronic sun exposure, and immune suppression. Diagnosing MCC utilizes a combination of morphology and immunohistochemistry. Merkel cell polyomavirus (MCPyV) is present in approximately 70-80% of MCCs and represents a key pathogenic driver in those MCCs. In contrast, MCPyV-negative MCCs arise through progressive accumulation of ultraviolet-light induced somatic mutations. Staging of MCC proceeds according to the American Joint Commission on Cancer (AJCC) 8th Edition, which utilizes features of the primary tumor together with regional lymph node(s) (clinically and/or pathologically detected) and/or distant metastases. Many potentially useful biomarkers have been studied to refine risk stratification in MCC. In recent years, the host immune infiltrate has been leveraged as immune checkpoint blockade has emerged as an efficacious mode of treatment for patients with advanced MCC.

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“…After WGA of single CTCs, analysis of copy number aberrations and MCPyV status in such cells showed that tumor tissue biopsies were mainly MCPyV + , whereas single CTCs from the same patient showed a more heterogeneous profile for detection of the polyomavirus. Heterogeneity of MCPyV status was already described, notably between primary and metastatic tumors 35 . These discrepancies might be explained by (i) a bias of amplification of the CTC genome, (ii) a loss of viral DNA upon cancer cell detachment and dissemination, or (iii) the presence of MCPyV − clones in metastases, suggested by the hit-and-run theory, as discussed previously 36 .…”

Section: Discussionmentioning

confidence: 84%

Circulating Tumor Cell Detection and Polyomavirus Status in Merkel Cell Carcinoma

Boyer¹,

Cayrefourcq²,

Garima³

et al. 2020

Sci Rep

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the incidence of Merkel cell carcinoma (Mcc), a rare and highly metastatic skin malignancy, has sharply increased in the last decade. clinical biomarkers are urgently needed for Mcc prognosis, treatment response monitoring, and early diagnosis of relapse. the clinical interest of circulating tumors cells (ctcs) has been validated in many solid cancers. the aim of this study was to compare ctc detection and characterization in blood samples of patients with Mcc using the cellSearch System and the RosetteSep -DEPArray workflow, an innovative procedure to enrich, detect and isolate single CTCs. In preliminary experiments (using spiked Mcc cell lines) both methods allowed detecting very few Mcc cells. In blood samples from 19 patients with MCC at different stages, CellSearch detected MCC CTCs in 26% of patients, and the R-D workflow in 42% of patients. The detection of CTC-positive patients increased to 52% by the cumulative positivity rate of both methodologies. Moreover, Merkel cell polyomavirus DnA, involved in Mcc oncogenesis, was detected in tumor biopsies, but not in all single CTCs from the same patient, reflecting the tumor heterogeneity. Our data demonstrate the possibility to detect, isolate and characterize ctcs in patients with Mcc using two complementary approaches.Merkel Cell Carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer, the incidence of which has been steadily increasing over the last decades 1,2 . It is one of the most lethal skin malignancies after melanoma 3 , and more frequently affects fair-skinned men with a median age of 70 years at diagnosis 4 . MCC usually appears as a rapidly growing red or purple nodule mostly located on UV-exposed areas (head, neck or upper limbs). Several risk factors have been identified, such as UV exposure, disease-or treatment-related immunosuppression, notably transplanted and HIV-infected patients 5 . A new virus belonging to the Polyomaviridae family and named Merkel cell polyomavirus (MCPyV) has been identified in some MCC tissue specimens 6 . The clonal integration of the viral DNA in the genome of MCC cells 7 suggests that this phenomenon is an early event occurring before malignant transformation 8 . This virus is present in most MCC (about 80% of patients) and seems to play a direct role in malignant transformation, most notably through the intervention of oncogenic proteins 6 . Indeed, MCPyV expresses the large T antigen and the small T antigen that display a strong oncogenic activity 9,10 . These oncogenic viral proteins are both expressed in MCPyV + MCC and seem to be necessary for the maintenance of MCPyV + MCC cell lines 11 . Conversely, MCPyV − MCC are characterized by higher number of mutations in key genes, a UV-mutational signature, and more chromosomal aberrations compared with MCPyV + tumors 8,12 , suggesting two distinct oncogenic pathways.Circulating tumor cells (CTCs) are considered as the real-time liquid biopsy for patients with cancer, described for the first time in 2010 13,14 . The stem-cell properties and sometimes the...

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Expression of Merkelcell polyomavirus (MCPyV) large T-antigen in Merkel cell carcinoma lymph node metastases predicts poor outcome

Cited by 11 publications

References 21 publications

Expression of 15‐lipoxygenase‐1 in Merkel cell carcinoma is linked to advanced disease

Expression of 15‐lipoxygenase‐1 in Merkel cell carcinoma is linked to advanced disease

Update on Merkel Cell Carcinoma

Circulating Tumor Cell Detection and Polyomavirus Status in Merkel Cell Carcinoma

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