Chronic lymphocytic leukaemia patients have a high risk of Merkel-cell polyomavirus DNA-positive Merkel-cell carcinoma (original) (raw)
Related papers
2010
Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma typically affecting the elderly. Only 5% to 10% of the patients are younger than 50 years at the time of the diagnosis. The purpose of this study was to compare the tumour and disease characteristics between exceptionally young and the typical elderly MCC population. Further, quantitative polymerase chain reaction analysis was used to study for Merkel cell polyomavirus (MCPyV) in their primary MCC tumours. Patients diagnosed with MCC in Finland from 1979 to 2004 were identified from the files of the Finnish Cancer Registry. Presence of MCPyV DNA in tumour samples was investigated using quantitative polymerase chain reaction. Six of 181 MCC patients were ≤50 years, with male-to-female ratio of 1:1. An altered immune condition state was observed in five patients. The Kaplan-Meier analysis showed a trend towards worse MCC-specific survival both in 5-and 10-year surveillance for younger patients. Five primary tumour tissue samples, available for analysis, contained MCPyV DNA. Our data shows that MCC, ≤50 years of age, is rarer then previously estimated. Moreover, our data showed marked differences both in patient demographics and in primary tumour characteristics as compared to surveys including older MCC patients. Course of disease seemed to be worse in the exceptionally young patients. All MCC primary tumours in this study contained MCPyV DNA.
Clinical Factors Associated With Merkel Cell Polyomavirus Infection in Merkel Cell Carcinoma
JNCI Journal of the National Cancer Institute, 2009
Merkel cell carcinoma is a rare malignancy of the skin. Integration of Merkel cell polyomavirus (MCPyV) DNA to the tumor genome is frequent in these cancers. The clinical consequences of MCPyV infection are unknown. We analyzed formalin-fixed paraffin-embedded Merkel cell carcinoma tissue samples from 114 of 207 patients diagnosed with Merkel cell carcinoma in Finland from 1979 to 2004 for the presence of MCPyV DNA with the use of polymerase chain reaction (PCR), quantitative PCR, and DNA sequencing and examined associations between tumor MCPyV DNA status and histopathologic factors and survival. The median follow-up time after Merkel cell carcinoma diagnosis for subjects who were alive was 9.9 years (range = 4.9-21.9 years). All P values are two-sided. MCPyV DNA was present in 91 carcinomas (79.8%). Compared with MCPyV DNA-negative cancers, MCPyV DNA-positive cancers were more often located in a limb (40.7% vs 8.7%, P = .015) and less frequent in patients who had regional nodal metastases at diagnosis (6.6% vs 21.7%, P = .043). Patients with MCPyV DNA-positive tumors had better overall survival than those with MCPyV DNA-negative tumors (5-year survival: 45.0% vs 13.0%, respectively; P < .001, two-sided log-rank test). MCPyV infection is associated with clinical outcomes in patients with Merkel cell carcinoma. These findings lend support to the hypothesis that viral infection is frequently associated with the pathogenesis of Merkel cell carcinoma.
Endocrine Pathology
Merkel cell carcinoma is a rare and aggressive primary neuroendocrine carcinoma of the skin, whose pathogenesis can be traced back to UV radiation damage or Merkel cell polyomavirus (MCPyV) infection. Despite some improvements on the characterization of the disease partly due to its increased incidence, crucial pathogenetic and prognostic factors still need to be refined. A consecutive series of 228 MCC from three hospitals in Turin was collected with the aim of both analyzing the apparent increase in MCC incidence in our area and investigating the distribution and prognostic role of clinical-pathological parameters, with a focus on MCPyV status, ALK tumor expression and tumor infiltrating lymphocytes (TILs). Review of morphology and conventional immunohistochemical staining was possible in 191 cases. In 50 cases, the expression of the novel neuroendocrine marker INSM1 was additionally assessed. Fourteen cases of MCC of unknown primary skin lesion were identified and separately anal...
Prospective study of Merkel cell polyomavirus and risk of Merkel cell carcinoma
2014
Merkel cell carcinoma (MCC) is a rare type of skin cancer that has a characteristically increased incidence among immunosuppressed subjects. The DNA of Merkel cell polyomavirus (MCV) is regularly found in most MCC tumors. We investigated whether Merkel cell polyomavirus (MCV) infection increases the risk for future MCC. Two large biobank cohorts (Southern Sweden Microbiology Biobank and the Janus Biobank), containing samples from 856,000 healthy donors, were linked to the Cancer Registries in Sweden and Norway to identify cases of MCC occurring up to 30 years after donation of a serum sample. For each of the 22 cases (nine males and 13 females), four matched controls were included. The serum samples were analyzed with an MCV neutralization assay and for IgG antibodies to MCV pseudovirions, using JC polyomavirus and cutaneous human papillomaviruses as control antigens. An increased risk for future MCC was associated both with high levels of MCV antibodies [OR 4.4, 95% CI 1.3-17.4] and with MCV neutralizing activity (OR 5.3, 95% CI 1.3-32.3). In males, MCV seropositivity was not associated to MCC risk, whereas the risk was strongly increased in females, both for high levels of MCV antibodies (OR 7.0, 95% CI 1.6-42.8) and for MCV neutralizing activity (OR 14.3, 95% CI 1.7-677). In conclusion, we found prospective evidence that MCV infection is associated with an increased risk for future MCC, in particular among females.
… journal of cancer, 2009
Recently, a new human polyoma virus has been identified in Merkel cell carcinomas (MCC). MCC is a highly aggressive neuroendocrine nonmelanoma skin cancer (NMSC) associated with immunosuppression. Clonal integration of this virus which was termed Merkel cell polyoma virus (MCPyV) was reported in a number of MCC. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are also NMSC and are the most frequent cancers in the setting of immunosuppression. A unique group of 56 NMSC from 11 immunosuppressed patients and 147 NMSC of 125 immunocompetent patients was tested for MCPyV by DNA PCR, targeting the Large T Antigen and the structural Viral Protein 1. NMSC included SCC, BCC and Bowen's disease (BD). In addition, normal skin and 89 colorectal cancers were tested. MCPyV specific sequences were significantly more frequently found in NMSC of immunosuppressed patients compared to immunocompetent patients (p < 0.001). In particular BD and BCC revealed a significant increased association of MCPyV of immunosuppressed patients (p 5 0.002 and p 5 0.006). Forty-seven of 147 (32%) sporadic NMSC were MCPyV positive. Interestingly, 37.5% (36/96) of sporadic BCC of immunocompetent patients were MCPyV positive. No MCPyV was detected within normal skin and only 3 out of 89 of additionally tested colorectal cancers were MCPyV positive. Our data show that MCPyV is a frequently reactivated virus in immunocompromized patients. How MCPyV contributes to the pathogenesis of NMSC, i.e., BD, SCC and BCC, in immunosuppressed patients and in addition, potentially to the pathogenesis of a subset of sporadic BCC needs further investigations. ' 2009 UICC Key words: nonmelanoma skin cancer (NMSC); merkel cell polyoma virus (MCPyV); immunosuppression Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are nonmelanoma skin cancers (NMSC) and in this order constitute the most frequent cancers associated with immunosuppression in transplant recipients. 1-6 According to the steadily increasing number of transplant operations performed each year in the European Union and the United States, post-transplant skin cancer is a leading medical issue in current transplantation medicine. To date a number of risk factors for the increasing number of NMSC under immunosuppression have been identified. 2 In addition to SCC and BCC, other NMSC, i.e., sebaceous cancers, cutaneous lymphomas and Merkel cell carcinomas (MCC) occur more frequently in post-transplant patients. 7,8 MCC has been described relatively recently and is a rare but very aggressive malignant neuroendocrine skin cancer of the elderly and immunosuppressed. 8-10 Very recently, Feng et al. reported the identification of a new human polyoma virus which was designated Merkel cell polyomavirus (MCPyV) based on its detection in MCC by digital transcriptome subtraction technique. 11 They reported the presence of MCPyV in 8 of 10 human MCC and also clonal integration of the viral DNA in 6 of 8 MCPyV-positive MCC.
Viruses, 2021
Because the incidence of Merkel cell carcinoma (MCC) has increased significantly during the last 10 years and it is recognized that Merkel cell polyomavirus (MCPyV) and ultraviolet (UV) radiation represent two different etiological inputs sharing clinical, histopathological, and prognostic similar features, although with different prognosis, this study investigated the detection of MCPyV in skin and lymph nodes with histological diagnosis of MCC. Formalin-fixed paraffin-embedded tissue (FFPE) were retrieved from archived specimens and MCPyV non-coding control region (NCCR) and viral capsid protein 1 (VP1) sequences were amplified and sequenced. Results provide an interesting observation concerning the discrepancy between the MCPyV DNA status in primary and metastatic sites: in fact, in all cases in which primary and metastatic lesions were investigated, MCPyV DNA was detected only in the primary lesions. Our data further support the “hit-and-run” theory, also proposed by other autho...
International Journal of Cancer, 2009
Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyomavirus. MCV DNA is integrated in 80% of Merkel cell carcinomas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its association with human diseases, we developed a monoclonal antibody that specifically recognizes endogenous and transfected MCV large T (LT) antigen. We show expression of MCV LT protein localized to nuclei of tumor cells from MCC having PCR quantified MCV genome at an average of 5.2 (range 0.8-14.3) T antigen DNA copies per cell. Expression of this putative viral oncoprotein in tumor cells provides the mechanistic underpinning supporting the notion that MCV causes a subset of MCC. In contrast, although 2.2% of 325 hematolymphoid malignancies surveyed also showed evidence for MCV infection by DNA PCR, none were positive at high viral copy numbers, and none of 173 lymphoid malignancies examined on tissue microarrays expressed MCV LT protein in tumor cells. As with some of the other human polyomaviruses, lymphocytes may serve as a tissue reservoir for MCV infection, but hematolymphoid malignancies associated with MCC are unlikely to be caused by MCV. ' 2009 UICC
Merkel cell polyomavirus infection in a patient with merkel cell carcinoma: a case report
Jundishapur journal of microbiology, 2015
Merkel cell carcinoma (MCC) is a rare and highly aggressive malignancy of the skin which occurs mainly in old people and is very uncommon in young individuals. A new tumor virus belonging to the Polyomaviridae family; Merkel Cell Polyomavirus (MCPyV) has recently been identified in more than 80% of MCCs. We conducted a retrospective review on the archives of the Department of Pathology; Imam Khomeini Hospital Cancer Institute affiliated to Tehran University of Medical Sciences to confirm the MCC samples and we found medical records and samples of a young case with MCC who developed leg skin and scalp tumor six and seven years after bone marrow transplantation, respectively. We analyzed patient formalin-fixed paraffin-embedded samples for the presence of MCPyV DNA using polymerase chain reaction (PCR) method, and the PCR amplicons were subjected to DNA sequencing. Merkel Cell Polyomavirus DNA was detected in both tumors from patient and sequence analysis of the viral LT3 region showe...