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Heikki Joensuu - One of the best experts on this subject based on the ideXlab platform.
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chronic lymphocytic leukaemia patients have a high risk of Merkel Cell polyomavirus dna positive Merkel Cell carcinoma
British Journal of Cancer, 2009Co-Authors: Virve Koljonen, Heli Kukko, Risto Sankila, Tom Böhling, Erkki Tukiainen, Eero Pukkala, Harri Sihto, Heikki JoensuuAbstract:Chronic lymphocytic leukaemia patients have a high risk of Merkel-Cell polyomavirus DNA-positive Merkel-Cell carcinoma
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chronic lymphocytic leukaemia patients have a high risk of Merkel Cell polyomavirus dna positive Merkel Cell carcinoma
British Journal of Cancer, 2009Co-Authors: Virve Koljonen, Heli Kukko, Risto Sankila, Tom Böhling, Erkki Tukiainen, Eero Pukkala, Harri Sihto, Heikki JoensuuAbstract:Immunosuppression and Merkel-Cell polyomavirus (MCPyV) infection may have a role in the pathogenesis of Merkel-Cell carcinoma (MCC), a rare neuroendocrine carcinoma of the skin. We studied incidence of chronic lymphocytic leukaemia (CLL) and MCC from the files of the Finnish Cancer Registry and the largest hospital of Finland, Helsinki University Central Hospital, from 1979 to 2006. Presence of MCPyV DNA in MCCs was investigated by quantitative PCR. We identified 4164 patients diagnosed with CLL and 172 diagnosed with MCC. Six patients diagnosed with both diseases were found; CLL was the first diagnosis in four cases and MCC in two. The standardised incidence ratio (SIR) for CLL after the diagnosis of MCC was highly elevated, 17.9 (95% confidence interval (CI), 2.2–64.6; P<0.001), and the SIR for MCC after the diagnosis of CLL was also elevated, 15.7 (3.2–46.0, P<0.01). Merkel-Cell polyomavirus DNA was present in all five MCCs with tumour tissue available for analysis. We conclude that patients diagnosed with CLL have a substantially increased risk for MCC, and vice versa. Merkel-Cell polyomavirus DNA is frequently present in MCCs that occur in CLL patients. Immunosuppression related with CLL and viral infection might explain the association between CLL and MCC.
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clinical factors associated with Merkel Cell polyomavirus infection in Merkel Cell carcinoma
Journal of the National Cancer Institute, 2009Co-Authors: Harri Sihto, Heli Kukko, Risto Sankila, Tom Böhling, Virve Koljonen, Heikki JoensuuAbstract:BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Virve Koljonen - One of the best experts on this subject based on the ideXlab platform.
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history of chronic inflammatory disorders increases the risk of Merkel Cell carcinoma but does not correlate with Merkel Cell polyomavirus infection
British Journal of Cancer, 2017Co-Authors: Helka Sahi, Tom Böhling, Virve Koljonen, Harri Sihto, Miia Artama, Eero PukkalaAbstract:We aimed to assess the connection between chronic inflammatory disorders (CIDs) and Merkel Cell carcinoma (MCC). Merkel Cell carcinoma cases diagnosed in 1978–2009 were extracted from the Finnish Cancer Registry and controls from the Population Registry. Information on reimbursed CIDs was linked to clinicopathological data including Merkel Cell polyomavirus (MCV) status by qPCR and immunohistochemistry for the large T antigen of MCV (LTA), Ki-67 and tumour-infiltrating lymphocytes. Chronic inflammatory disorders increased the risk of MCC significantly (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.03–1.88), specifically connective tissue/systemic diseases (OR 1.75, 95% CI 1.09–1.80) and diabetic conditions (OR 1.51, 95% CI 1.03–2.22). Chronic inflammatory disorders associated with larger tumour diameter (P=0.02) and higher Ki-67 expression (P=0.005). The expression of LTA was seen significantly more often in the absence of CIDs (P=0.05). Patients with CID are at significantly higher risk for aggressive MCC. Merkel Cell polyomavirus positivity is more common in MCC patients unafflicted by CID.
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chronic lymphocytic leukaemia patients have a high risk of Merkel Cell polyomavirus dna positive Merkel Cell carcinoma
British Journal of Cancer, 2009Co-Authors: Virve Koljonen, Heli Kukko, Risto Sankila, Tom Böhling, Erkki Tukiainen, Eero Pukkala, Harri Sihto, Heikki JoensuuAbstract:Chronic lymphocytic leukaemia patients have a high risk of Merkel-Cell polyomavirus DNA-positive Merkel-Cell carcinoma
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chronic lymphocytic leukaemia patients have a high risk of Merkel Cell polyomavirus dna positive Merkel Cell carcinoma
British Journal of Cancer, 2009Co-Authors: Virve Koljonen, Heli Kukko, Risto Sankila, Tom Böhling, Erkki Tukiainen, Eero Pukkala, Harri Sihto, Heikki JoensuuAbstract:Immunosuppression and Merkel-Cell polyomavirus (MCPyV) infection may have a role in the pathogenesis of Merkel-Cell carcinoma (MCC), a rare neuroendocrine carcinoma of the skin. We studied incidence of chronic lymphocytic leukaemia (CLL) and MCC from the files of the Finnish Cancer Registry and the largest hospital of Finland, Helsinki University Central Hospital, from 1979 to 2006. Presence of MCPyV DNA in MCCs was investigated by quantitative PCR. We identified 4164 patients diagnosed with CLL and 172 diagnosed with MCC. Six patients diagnosed with both diseases were found; CLL was the first diagnosis in four cases and MCC in two. The standardised incidence ratio (SIR) for CLL after the diagnosis of MCC was highly elevated, 17.9 (95% confidence interval (CI), 2.2–64.6; P<0.001), and the SIR for MCC after the diagnosis of CLL was also elevated, 15.7 (3.2–46.0, P<0.01). Merkel-Cell polyomavirus DNA was present in all five MCCs with tumour tissue available for analysis. We conclude that patients diagnosed with CLL have a substantially increased risk for MCC, and vice versa. Merkel-Cell polyomavirus DNA is frequently present in MCCs that occur in CLL patients. Immunosuppression related with CLL and viral infection might explain the association between CLL and MCC.
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clinical factors associated with Merkel Cell polyomavirus infection in Merkel Cell carcinoma
Journal of the National Cancer Institute, 2009Co-Authors: Harri Sihto, Heli Kukko, Risto Sankila, Tom Böhling, Virve Koljonen, Heikki JoensuuAbstract:BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Paul Nghiem - One of the best experts on this subject based on the ideXlab platform.
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Merkel Cell carcinoma
Nature Reviews Disease Primers, 2017Co-Authors: J C Becker, James A Decaprio, Andreas Stang, Lorenzo Cerroni, Celeste Lebbé, Michael Veness, Paul NghiemAbstract:Merkel Cell carcinoma (MCC) is a rare, highly metastatic skin cancer. MCC pathogenesis is associated with either the presence of Merkel Cell polyomavirus or chronic exposure to ultraviolet light, which can cause a characteristic pattern of multiple DNA mutations. Merkel Cell carcinoma (MCC) is a rare but highly aggressive skin cancer with neuroendocrine features. MCC pathogenesis is associated with either the presence of Merkel Cell polyomavirus or chronic exposure to ultraviolet light (UV), which can cause a characteristic pattern of multiple DNA mutations. Notably, in the Northern hemisphere, the majority of MCC cases are of viral aetiology; by contrast, in areas with high UV exposure, UV-mediated carcinogenesis is predominant. The two aetiologies share similar clinical, histopathological and prognostic characteristics. MCC presents with a solitary cutaneous or subcutaneous nodule, most frequently in sun-exposed areas. In fact, UV exposure is probably involved in both viral-mediated and non-viral-mediated carcinogenesis, by contributing to immunosuppression or DNA damage, respectively. Confirmation of diagnosis relies on analyses of histological features and immunological marker expression profiles of the lesion. At primary diagnosis, loco-regional metastases are already present in ∼30% of patients. Excision of the tumour is the first-line therapy; if not feasible, radiotherapy can often effectively control the disease. Chemotherapy was the only alternative in advanced-stage or refractory MCC until several clinical trials demonstrated the efficacy of immune-checkpoint inhibitors.
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pd 1 blockade with pembrolizumab in advanced Merkel Cell carcinoma
The New England Journal of Medicine, 2016Co-Authors: Paul Nghiem, Shailender Bhatia, Evan J Lipson, Ragini R Kudchadkar, Natalie J Miller, Lakshmanan Annamalai, Sneha Berry, Elliot Chartash, Adil Daud, Steven P FlingAbstract:BackgroundMerkel-Cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-Cell polyomavirus (MCPyV). Advanced Merkel-Cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T Cells express PD-1. MethodsIn this multicenter, phase 2, noncontrolled study, we assigned adults with advanced Merkel-Cell carcinoma who had received no previous systemic therapy to receive pembrolizumab (anti–PD-1) at a dose of 2 mg per kilogram of body weight every 3 weeks. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Efficacy was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing. ResultsA total of 26 patients received at least one dose of pembrolizumab. The objective response rate among the 25 patient...
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identification and validation of a novel mature microrna encoded by the Merkel Cell polyomavirus in human Merkel Cell carcinomas
Journal of Clinical Virology, 2011Co-Authors: Sherry Lee, Kelly G Paulson, Elizabeth P Murchison, Olga K Afanasiev, Can Alkan, Helen J Leonard, David R Byrd, Gregory J Hannon, Paul NghiemAbstract:Background Merkel Cell polyomavirus (MCPyV) is present in approximately 80% of human Merkel Cell carcinomas (MCCs). A previous in silico prediction suggested MCPyV encodes a microRNA (miRNA) that may regulate Cellular and viral genes.
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association of Merkel Cell polyomavirus specific antibodies with Merkel Cell carcinoma
Journal of the National Cancer Institute, 2009Co-Authors: Joseph J Carter, Kelly G Paulson, Danielle Miranda, Lisa G Johnson, Bianca D Lemos, Ashley H Warcola, Jayasri G Iyer, Gregory C. Wipf, Margaret M. Madeleine, Paul NghiemAbstract:Background Merkel Cell polyomavirus (MCPyV) has been detected in approximately 75% of patients with the rare skin cancer Merkel Cell carcinoma. We investigated the prevalence of antibodies against MCPyV in the general population and the association between these antibodies and Merkel Cell carcinoma. Methods Multiplex antibody-binding assays were used to assess levels of antibodies against polyomaviruses in plasma. MCPyV VP1 antibody levels were determined in plasma from 41 patients with Merkel Cell carcinoma and 76 matched control subjects. MCPyV DNA was detected in tumor tissue specimens by quantitative polymerase chain reaction. Seroprevalence of polyomavirus-specific antibodies was determined in 451 control subjects. MCPyV strain – specific antibody recognition was investigated by replacing coding sequences from MCPyV strain 350 with those from MCPyV strain w162. Results We found that 36 (88%) of 41 patients with Merkel Cell carcinoma carried antibodies against VP1 from MCPyV w162 compared with 40 (53%) of the 76 control subjects (odds ratio adjusted for age and sex = 6.6, 95% confidence interval [CI] = 2.3 to 18.8). MCPyV DNA was detectable in 24 (77%) of the 31 Merkel Cell carcinoma tumors available, with 22 (92%) of these 24 patients also carrying antibodies against MCPyV. Among 451 control subjects from the general population, prevalence of antibodies against human polyomaviruses was 92% (95% CI = 89% to 94%) for BK virus, 45% (95% CI = 40% to 50%) for JC virus, 98% (95% CI = 96% to 99%) for WU polyomavirus, 90% (95% CI = 87% to 93%) for KI polyomavirus, and 59% (95% CI = 55% to 64%) for MCPyV. Few case patients had reactivity against MCPyV strain 350; however, indistinguishable reactivities were found with VP1 from strain 350 carrying a double mutation (residues 288 and 316) and VP1 from strain w162. Conclusion Infection with MCPyV is common in the general population. MCPyV, but not other human polyomaviruses, appears to be associated with Merkel Cell carcinoma.
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Merkel Cell polyomavirus is more frequently present in north american than australian Merkel Cell carcinoma tumors
Journal of Investigative Dermatology, 2009Co-Authors: Kelly M Garneski, Ashley H Warcola, Helen J Leonard, Qinghua Feng, Nancy B Kiviat, Paul NghiemAbstract:TO THE EDITOR Merkel Cell carcinoma (MCC) is an increasingly common neuroendocrine cancer of the skin. MCC is an aggressive malignancy that is a significant cause of non-melanoma skin cancer deaths. Although the genetics of MCC are poorly characterized, it is well established that MCC is associated with advanced age and ultraviolet-light exposure. MCC is also linked to immune suppression; 8% of MCC patients are chronically immunosuppressed, which is a 16-fold over-representation(Heath et al., 2008). In particular, MCC is linked to T Cell dysfunction associated with malignant, infectious and iatrogenic causes(Heath et al., 2008),(Engels et al., 2002),(Miller and Rabkin, 1999). Recently, Feng et al. described a novel polyomavirus that is associated with Merkel Cell carcinoma(Feng et al., 2008). This virus, named Merkel Cell polyomavirus (MCPyV), was present in 8 of 10 MCC tumors as compared to 1 of 15 normal skin controls. Several clues suggest a possible functional role for this virus in cancer. MCPyV shares key features with the SV40 polyomavirus, an oncogenic virus in animals, such as the predicted ability of a viral protein to bind and inactivate the tumor suppressor Rb. Furthermore, MCPyV DNA was reported to be monoclonally integrated into six of the tumors, which implies that viral integration was an early event in MCC carcinogenesis and occurred before tumor expansion. To confirm this recent discovery, we used quantitative real-time PCR to detect the presence or absence of Merkel Cell polyomavirus DNA in 37 MCC tumor specimens originating from 37 patients in North America and Australia. Two primer sets targeting MCPyV, but not other known human polyomaviruses, were used. One set amplifies the region corresponding to the common portion of large and small T antigen (nucleotides 236–374 of the “MCV350” sequence, [{"type":"entrez-nucleotide","attrs":{"text":"EU375803","term_id":"164664905"}}EU375803]) and the second set amplifies a portion of the large T antigen surrounding a BamH1 restriction site (nucleotides 1083–1181). Products of the second set were digested with BamH1 and resolved on an acrylamide gel to verify product specificity. For a comparison control gene, primers were designed to amplify a gene on chromosome 2 (the TPO gene) because chromosome 2 is usually stable and only rarely gained or lost in MCC tumors(Van Gele et al., 1998). Serial dilutions were employed to calibrate the relative efficiency of the PCR reactions and ensure that the delta-delta CT method could be used to determine relative amounts of DNA between the viral and control genomic targets. The sensitivity of the real-time platform allowed us to detect levels of the viral gene as low as one five-thousandth the level of the control gene. All reactions were done in triplicate, and water and pooled human male lymphocyte DNA were included as negative controls. We also performed the PCR under less stringent conditions (lower annealing temperature). Under these conditions, we did not detect additional MCPyV positive tumors, but cannot rule out the possibility of presence of a strain variant in the negative tumors. We found that 16 of 37 Merkel Cell carcinoma tumor tissues were positive for Merkel Cell polyomavirus DNA (43%). Interestingly, the proportion of tumors positive for MCPyV was much higher in tumors originating from North America than those originating from Australia (Figure 1). Among North American MCC specimens, 11 of 16 tumors (69%) were positive, which is similar to the initial report of 8 of 10 tumors(Feng et al., 2008). In contrast, only 5 of 21 Australian MCC specimens (24%) were positive for MCPyV. Additionally, we tested 15 primary squamous Cell carcinoma (SCC) tumors, and 15 apparently normal sun-exposed skin samples, from 30 North American patients without MCC. These patients had a similar age and gender distribution to the MCC patients. MCPyV was not detected in any of the normal skin DNA, but was present in 2 of 15 SCC tumors (13%). Figure 1 Presence of MCPyV DNA in samples from North America (NA) and Australia (AU) The MCC tumor tissues tested included primaries and metastases. We observed MCPyV in 5 of 8 primary tumors, 3 of 13 recurrences, 7 of 15 nodal metastases, and in the single studied distant metastasis. Outcome data were available for 30 of the 37 patients. In this subset, no survival difference was noted between virus positive and virus negative tumors using Kaplan-Meier analysis (data not shown). We found wide variation in the amount of viral DNA present. Indeed, the amount of viral DNA relative to control DNA varied over five orders of magnitude among the virus-positive MCC tumors (Figure 2). Figure 2 Marked variability of Merkel Cell polyomavirus DNA quantity among MCC tumors These data confirm the important discovery of Feng et al. that a polyomavirus is associated with Merkel Cell carcinoma. Virus was present in MCC tumors, and was present in a similar percentage of North American tumors as previously reported. Our data further present the interesting observation that North American MCC tumors are more frequently MCPyV positive than Australian MCC tumors. This difference may be due to the increased sun exposure in Australia, making a possible viral contribution less frequent. We cannot exclude the possibility that a different and unknown MCPyV strain, not detectable with our specific assay, or perhaps an alternate virus is present in the Australian Merkel Cell carcinomas. The majority of Australian samples were nodal metastases, whereas most North American samples were primaries. However, we believe this is unlikely to account for our observed difference because for two North American tumors both primary and nodal tissues were available, and for each tumor both the primary and nodal tissues were similarly virus positive (data not shown). It is important to note that most of the Australian tumor specimens were collected in the 1990’s and most North American specimens were collected after the year 2000. However, DNA quality from the Australian specimens was exCellent both by spectrophotometry and PCR of control genes. Our observed percentages may over- or under-represent the true prevalence of MCPyV in MCC tumors because our left-over surgical specimens are biased towards more advanced Merkel Cell carcinoma than average. This was true of both the Australian and North American specimens. 2 of 15 SCC samples had detectable MCPyV DNA. A larger study is required to determine whether MCPyV is reproducibly more often present in SCC tumors than in normal skin. Merkel Cell polyomavirus represents an exciting direction for future studies in two major areas. The first area is functional characterization of the Merkel Cell polyomavirus and determination if it expresses biologically active viral proteins and whether it is in fact involved in the generation or maintenance of MCC tumors. The second major direction is an epidemiologic characterization of the prevalence of MCPyV in healthy people and in various tumors as this virus may plausibly be associated with other human diseases or malignancies.
Harri Sihto - One of the best experts on this subject based on the ideXlab platform.
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history of chronic inflammatory disorders increases the risk of Merkel Cell carcinoma but does not correlate with Merkel Cell polyomavirus infection
British Journal of Cancer, 2017Co-Authors: Helka Sahi, Tom Böhling, Virve Koljonen, Harri Sihto, Miia Artama, Eero PukkalaAbstract:We aimed to assess the connection between chronic inflammatory disorders (CIDs) and Merkel Cell carcinoma (MCC). Merkel Cell carcinoma cases diagnosed in 1978–2009 were extracted from the Finnish Cancer Registry and controls from the Population Registry. Information on reimbursed CIDs was linked to clinicopathological data including Merkel Cell polyomavirus (MCV) status by qPCR and immunohistochemistry for the large T antigen of MCV (LTA), Ki-67 and tumour-infiltrating lymphocytes. Chronic inflammatory disorders increased the risk of MCC significantly (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.03–1.88), specifically connective tissue/systemic diseases (OR 1.75, 95% CI 1.09–1.80) and diabetic conditions (OR 1.51, 95% CI 1.03–2.22). Chronic inflammatory disorders associated with larger tumour diameter (P=0.02) and higher Ki-67 expression (P=0.005). The expression of LTA was seen significantly more often in the absence of CIDs (P=0.05). Patients with CID are at significantly higher risk for aggressive MCC. Merkel Cell polyomavirus positivity is more common in MCC patients unafflicted by CID.
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chronic lymphocytic leukaemia patients have a high risk of Merkel Cell polyomavirus dna positive Merkel Cell carcinoma
British Journal of Cancer, 2009Co-Authors: Virve Koljonen, Heli Kukko, Risto Sankila, Tom Böhling, Erkki Tukiainen, Eero Pukkala, Harri Sihto, Heikki JoensuuAbstract:Chronic lymphocytic leukaemia patients have a high risk of Merkel-Cell polyomavirus DNA-positive Merkel-Cell carcinoma
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chronic lymphocytic leukaemia patients have a high risk of Merkel Cell polyomavirus dna positive Merkel Cell carcinoma
British Journal of Cancer, 2009Co-Authors: Virve Koljonen, Heli Kukko, Risto Sankila, Tom Böhling, Erkki Tukiainen, Eero Pukkala, Harri Sihto, Heikki JoensuuAbstract:Immunosuppression and Merkel-Cell polyomavirus (MCPyV) infection may have a role in the pathogenesis of Merkel-Cell carcinoma (MCC), a rare neuroendocrine carcinoma of the skin. We studied incidence of chronic lymphocytic leukaemia (CLL) and MCC from the files of the Finnish Cancer Registry and the largest hospital of Finland, Helsinki University Central Hospital, from 1979 to 2006. Presence of MCPyV DNA in MCCs was investigated by quantitative PCR. We identified 4164 patients diagnosed with CLL and 172 diagnosed with MCC. Six patients diagnosed with both diseases were found; CLL was the first diagnosis in four cases and MCC in two. The standardised incidence ratio (SIR) for CLL after the diagnosis of MCC was highly elevated, 17.9 (95% confidence interval (CI), 2.2–64.6; P<0.001), and the SIR for MCC after the diagnosis of CLL was also elevated, 15.7 (3.2–46.0, P<0.01). Merkel-Cell polyomavirus DNA was present in all five MCCs with tumour tissue available for analysis. We conclude that patients diagnosed with CLL have a substantially increased risk for MCC, and vice versa. Merkel-Cell polyomavirus DNA is frequently present in MCCs that occur in CLL patients. Immunosuppression related with CLL and viral infection might explain the association between CLL and MCC.
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clinical factors associated with Merkel Cell polyomavirus infection in Merkel Cell carcinoma
Journal of the National Cancer Institute, 2009Co-Authors: Harri Sihto, Heli Kukko, Risto Sankila, Tom Böhling, Virve Koljonen, Heikki JoensuuAbstract:BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Tom Böhling - One of the best experts on this subject based on the ideXlab platform.
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history of chronic inflammatory disorders increases the risk of Merkel Cell carcinoma but does not correlate with Merkel Cell polyomavirus infection
British Journal of Cancer, 2017Co-Authors: Helka Sahi, Tom Böhling, Virve Koljonen, Harri Sihto, Miia Artama, Eero PukkalaAbstract:We aimed to assess the connection between chronic inflammatory disorders (CIDs) and Merkel Cell carcinoma (MCC). Merkel Cell carcinoma cases diagnosed in 1978–2009 were extracted from the Finnish Cancer Registry and controls from the Population Registry. Information on reimbursed CIDs was linked to clinicopathological data including Merkel Cell polyomavirus (MCV) status by qPCR and immunohistochemistry for the large T antigen of MCV (LTA), Ki-67 and tumour-infiltrating lymphocytes. Chronic inflammatory disorders increased the risk of MCC significantly (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.03–1.88), specifically connective tissue/systemic diseases (OR 1.75, 95% CI 1.09–1.80) and diabetic conditions (OR 1.51, 95% CI 1.03–2.22). Chronic inflammatory disorders associated with larger tumour diameter (P=0.02) and higher Ki-67 expression (P=0.005). The expression of LTA was seen significantly more often in the absence of CIDs (P=0.05). Patients with CID are at significantly higher risk for aggressive MCC. Merkel Cell polyomavirus positivity is more common in MCC patients unafflicted by CID.
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chronic lymphocytic leukaemia patients have a high risk of Merkel Cell polyomavirus dna positive Merkel Cell carcinoma
British Journal of Cancer, 2009Co-Authors: Virve Koljonen, Heli Kukko, Risto Sankila, Tom Böhling, Erkki Tukiainen, Eero Pukkala, Harri Sihto, Heikki JoensuuAbstract:Chronic lymphocytic leukaemia patients have a high risk of Merkel-Cell polyomavirus DNA-positive Merkel-Cell carcinoma
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chronic lymphocytic leukaemia patients have a high risk of Merkel Cell polyomavirus dna positive Merkel Cell carcinoma
British Journal of Cancer, 2009Co-Authors: Virve Koljonen, Heli Kukko, Risto Sankila, Tom Böhling, Erkki Tukiainen, Eero Pukkala, Harri Sihto, Heikki JoensuuAbstract:Immunosuppression and Merkel-Cell polyomavirus (MCPyV) infection may have a role in the pathogenesis of Merkel-Cell carcinoma (MCC), a rare neuroendocrine carcinoma of the skin. We studied incidence of chronic lymphocytic leukaemia (CLL) and MCC from the files of the Finnish Cancer Registry and the largest hospital of Finland, Helsinki University Central Hospital, from 1979 to 2006. Presence of MCPyV DNA in MCCs was investigated by quantitative PCR. We identified 4164 patients diagnosed with CLL and 172 diagnosed with MCC. Six patients diagnosed with both diseases were found; CLL was the first diagnosis in four cases and MCC in two. The standardised incidence ratio (SIR) for CLL after the diagnosis of MCC was highly elevated, 17.9 (95% confidence interval (CI), 2.2–64.6; P<0.001), and the SIR for MCC after the diagnosis of CLL was also elevated, 15.7 (3.2–46.0, P<0.01). Merkel-Cell polyomavirus DNA was present in all five MCCs with tumour tissue available for analysis. We conclude that patients diagnosed with CLL have a substantially increased risk for MCC, and vice versa. Merkel-Cell polyomavirus DNA is frequently present in MCCs that occur in CLL patients. Immunosuppression related with CLL and viral infection might explain the association between CLL and MCC.
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clinical factors associated with Merkel Cell polyomavirus infection in Merkel Cell carcinoma
Journal of the National Cancer Institute, 2009Co-Authors: Harri Sihto, Heli Kukko, Risto Sankila, Tom Böhling, Virve Koljonen, Heikki JoensuuAbstract:BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.