Merkel Cell Polyomavirus Positivity Research Articles

Clinicopathological characteristics and prognosis of Merkel cell carcinoma: a single-center retrospective study in Korea.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin with high mortality. However, its clinical characteristics in Asian patients remain uncertain owing to its low incidence. To analyze the clinicopathological features of MCC and identify factors associated with its prognosis. The medical records of 62 patients with MCC were retrospectively reviewed. Data on clinical features, survival outcomes, prognostic factors, histopathology and immunohistochemical profile of the patients were collected and analyzed. Merkel cell polyomavirus status was evaluated using immunohistochemistry. The incidence of MCC significantly increased over time. The mean duration of follow-up was 51.2months, with an overall 5-year survival of 80.6%. More female patients with MCC were identified than male patients (1.3:1). Approximately half of the patients had stage I disease at the time of initial presentation. The primary tumor was frequently located in the lower extremities (40.3%), followed by the head and neck (32.3%), upper extremities (22.6%), and the trunk (4.8%). Male sex was associated with poorer overall survival (p = 0.003). Post-resection adjuvant radiotherapy significantly improved the overall survival (p = 0.023). Sentinel lymph node biopsy during surgery ameliorated the progression-free survival (p = 0.036) in patients with stage I or II cancer. Lymphovascular and perineural invasion were associated with a poor prognosis. Old age, immunohistochemical profiles, and Merkel cell polyomavirus-positivity were not associated with prognosis. Post-surgical adjuvant radiotherapy and sentinel lymph node biopsy significantly improve the course of MCC.

33904 Early onset Merkel cell carcinoma in patients with XMEN disease

Background: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer frequently caused by Merkel cell polyomavirus (MCPyV). The median age for MCC diagnosis is 75 years, and MCC is vanishingly rare in patients under 40. We describe 3 patients with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN) who developed MCC before age 25. XMEN disease is a rare immunodeficiency associated with lymphoma and caused by mutations in the magnesium transporter 1 (MAGT1) gene. Methods: Retrospective chart review for 3 individuals with MCC and XMEN disease. Results: Patient 1 had a history of recurrent childhood infections and splenomegaly and presented at 14 years of age with metastatic MCC that was treated with high-intensity chemotherapy, radiation therapy, and an autologous stem cell transplant. Patient 2 had a history of chronic EBV viremia and recurrent infections and presented at age 22 with Stage III MCC that was treated with surgical resection and radiotherapy. Patient 3 had a history of thrombocytopenia, splenomegaly, and recurrent infections and developed Stage I MCC at age 24 that was treated with surgical resection and radiotherapy. All three patients had MCPyV positive tumors. The patients are alive and tumor-free 13, 4, and 9 years after diagnosis, respectively. Conclusion: Although immunosuppression increases MCC incidence, XMEN disease is associated with a risk for early onset MCC not observed in other primary immunodeficiencies. The MCPyV positivity and prolonged survival in these 3 cases is also atypical for immunosuppressed patients with MCC.

ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival.

Merkel cell carcinoma (MCC) is a rare skin cancer with only limited therapeutic options for advanced disease. We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel cell polyomavirus (MCPyV) positivity. In this study, we investigated whether ALK receptor is active in MCC tumor samples and MCC cell lines, and whether ALK would be a prospective treatment target in MCC. We utilized tissue microarrays constructed from 136 primary MCC tumor samples as well as nine previously established MCC cell lines to determine the presence of ALK and phosphorylated ALK (p-ALK) via immunohistochemistry. Almost half of the analyzed MCC tumors displayed ALK phosphorylation (47.8%). Analysis of MCC tumor samples revealed that the presence of p-ALK correlated to MCPyV positivity, younger age, nonexistence of metastases at diagnosis and ultimately to better MCC-specific survival. In contrast to MCC tumor samples only two out of nine MCC cell lines showed only low ALK phosphorylation by immunohistochemistry. Our study reveals clear disparity in ALK activity between patient derived tumors and cell line samples and therefore, more advanced disease models such as xenografts are necessary to resolve whether ALK is a useful treatment target in MCC.

Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas.

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.

Virus-positive Merkel Cell Carcinoma Is an Independent Prognostic Group with Distinct Predictive Biomarkers.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that can be divided into two classes: virus-positive (VP) MCC, associated with oncogenic Merkel cell polyomavirus (MCPyV); and virus-negative (VN) MCC, associated with photodamage. We classified 346 MCC tumors from 300 patients for MCPyV using a combination of IHC, ISH, and qPCR assays. In a subset of tumors, we profiled mutation status and expression of cancer-relevant genes. MCPyV and molecular profiling results were correlated with disease-specific outcomes. Potential prognostic biomarkers were further validated by IHC. A total of 177 tumors were classified as VP-MCC, 151 tumors were VN-MCC, and 17 tumors were indeterminate. MCPyV positivity in primary tumors was associated with longer disease-specific and recurrence-free survival in univariate analysis, and in multivariate analysis incorporating age, sex, immune status, and stage at presentation. Prioritized oncogene or tumor suppressor mutations were frequent in VN-MCC but rare in VP-MCC. TP53 mutation developed with recurrence in one VP-MCC case. Importantly, for the first time we find that VP-MCC and VN-MCC display distinct sets of prognostic molecular biomarkers. For VP-MCC, shorter survival was associated with decreased expression of immune markers including granzyme and IDO1. For VN-MCC, shorter survival correlated with high expression of several genes including UBE2C. MCPyV status is an independent prognostic factor for MCC. Features of the tumor genome, transcriptome, and microenvironment may modify prognosis in a manner specific to viral status. MCPyV status has clinicopathologic significance and allows for identification of additional prognostic subgroups.

Large nuclear size correlated with better overall survival, Merkel cell polyomavirus positivity, and terminal deoxynucleotidyl transferase expression in Merkel cell carcinoma

To the Editor: The histologic appearance of Merkel cell polyomavirus (MCPyV)-positive Merkel cell carcinoma (MCC) has been reported to be distinctive: more uniform, round nuclei and less cytoplasm than cells in MCPyV-negative tumors.1,2 In most of these studies, however, the described morphologic differences were identified by light microscopy, and morphometric analysis was done on a limited number of cases.1,3 Extraction of nuclear features by computational methods from high-resolution whole-slide digital scans of histologic slides has been shown to improve accuracy and consistency.

Merkel Cell Polyomavirus Gene Expression and Mutational Analysis of Large Tumor Antigen in Non-Merkel Cell Carcinoma Tumors of Iranian Patients

Introduction: The presence of Merkel cell polyomavirus (MCPyV) was identified in Merkel cell carcinoma (MCC). However, there was sparse information on the link of other common nonmelanoma skin cancers – basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – to MCPyV infection. The current study describes the phylogenetic information of MCPyV isolated from Iranian non-MCC (nonmelanoma skin cancers) focusing on tumorigenesis of mutations in large tumor (LT) antigen (LT-Ag) fragment. Methods: Sixty patients with BCC and 20 patients with SCC were included in this study (48 males and 32 females; average age 65 years). The MCPyV-DNA copy number in positive samples was measured by quantitative real-time PCR. Then, mutational analysis of the MCPyV LT gene was carried out by direct sequencing. Results: While MCPyV DNA was detected in 6 (10%) of 60 BCC samples, no viral genome was found in SCCs. There was no distinct association of MCPyV positivity with gender, age, or type of tumor (BCC or SCC) (p value >0.05). Quantitative real-time PCR revealed that the median number of viral DNA copies per cell was 0.7 in 6 MCPyV-positive BCC samples. Furthermore, full-length LT-Ag sequencing of positive samples indicated no stop codon or frameshift mutations compared to reference sequences. Conclusion: Considering the important role of the LT-Ag in the pathogenicity of MCPyV, non-synonymous mutations compared with the reference proteins triggered relevant amino acid substitutions. Overall, the results showed no tumor-associated mutations in the LT-Ag sequence of MCPyVs from positive samples.

Merkel cell polyomavirus DNA sequences in the blood of healthy population of Pakistan.

Aim: This study aimed at detecting and quantifying Merkel cell polyomavirus (MCPyV) viral loads in the peripheral blood of healthy Pakistani individuals. Patients & methods: A total of 221 whole blood samples obtained from healthy individuals were examined by qPCR. Results & conclusion: MCPyV was detected in the peripheral blood of 31.2% healthy individuals. The rate of MCPyV positivity decreased from young (36%), to middle (33.7%) and elder (25.3%) age groups. Our data revealed higher prevalence of MCPyV in women (43.93%) than men (25.80%). The MCPyV viral load was calculated in the range of 0.06 -11copies/ng of isolated DNA. The MCPyV viral load increased from young (median=3.35) to elder (median=5.66) age groups. The MCPyV circulate at a higher frequency by residing dormant in certain blood cells, which might act as potential vehicles for the spread of MCPyV infection among general population.

The expression of terminal deoxynucleotidyl transferase and paired box gene 5 in Merkel cell carcinomas and its relation to the presence of Merkel cell polyomavirus DNA.

Merkel cell carcinoma (MCC) tumor samples frequently express B-lymphoid lineage markers. However, the reasons for expression of specific B-lymphoid lineage markers are still unclear. We studied the expression of TdT and PAX5 (two B-cell lymphoid lineage markers) in a large pool of MCC tissue microarray samples. Immunoexpression and staining intensities of TdT and Pax-5 were statistically correlated with patient, tumor, Merkel cell polyomavirus (MCV), and disease-specific parameters. In a cohort of 117 MCC patients and their corresponding tumor samples, TdT was expressed in 37 (31.6%) samples and PAX5 in 26 (22.2%). Simultaneous immunostaining for TdT and PAX5 was observed in 13 (11.1%) samples. A statistically significant relationship was observed between MCV virus copy number and positive TdT expression (P = 0.0056). Similarly, a significant relationship was also observed between positive TdT and tumor MCV virus positivity (P = 0.000495). We observed frequent TdT and PAX5 immunoexpression in MCC tumor samples. However, simultaneous immunoexpression of these markers was scarce. TdT expression was statistically significantly associated with MCV positivity. The absence of a statistically significant association between tumor parameters and disease progression markers undermines the systemic use of these markers in clinical practice.

Age and Gender Associations of Virus Positivity in Merkel Cell Carcinoma Characterized Using a Novel RNA In Situ Hybridization Assay.

Purpose: Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine tumor of the skin. Merkel cell polyomavirus (MCPyV) plays an oncogenic role in the majority of MCCs. Detection of MCPyV in MCCs has diagnostic utility and prognostic potential. We investigated whether RNAscope, an RNA in situ hybridization (ISH) assay for detection of RNA transcripts in tissues, is useful for MCPyV detection.Experimental Design: We applied an RNAscope probe targeting MCPyV T antigen transcripts on tissue microarrays (TMA) and whole-tissue sections encompassing 87 MCCs from 75 patients, 14 carcinomas of other types, and benign tissues. For comparison, qPCR was performed on 57 cases of MCC from 52 patients.Results: RNA-ISH demonstrated the presence of MCPyV in 37 of 75 cases (49.3%). Notably, tumors from younger patients (<73 years) had a significantly higher virus positivity than those from elderly patients (≥73 years; 64.9% vs. 34.2%, P = 0.011). Female patients had a higher positive rate of MCPyV than male patients (66.7% vs. 39.6%, P = 0.032). Data from both RNA-ISH and qPCR were available for 57 samples. Considering MCPyV qPCR as the gold standard for determining MCPyV status, RNAscope had 100% sensitivity and 100% specificity. There was a strong correlation between qPCR copy number and RNA-ISH product score (Spearman correlation coefficient R2 = 0.932, P < 0.0001).Conclusions: RNA-ISH is comparably sensitive to qPCR for detection of MCPyV and allows for correlation with tissue morphology. This study also reveals a significant association between age, gender, and MCPyV positivity. Clin Cancer Res; 23(18); 5622-30. ©2017 AACR.

Detection of Merkel Cell Polyomavirus in Respiratory Tract Specimens

Objective: The role of Merkel cell polyomavirus (MCPyV) as a respiratory pathogen is controversial. The aim of this study was to determine the prevalence of MCPyV in patients with acute respiratory diseases and chronic lung diseases, including lung cancer, in order to evaluate the association between MCPyV infection and respiratory diseases. Methods: This study included 221 specimens (133 nasopharyngeal swabs and 88 lung biopsy specimens) obtained from patients with acute respiratory diseases and chronic lung diseases, including lung cancer. The detection of MCPyV was performed via nested polymerase chain reaction. Results: MCPyV positivity was 4.3% on average. All nasopharyngeal specimens were obtained from patients with acute respiratory diseases, and 8.2% of them were MCPyV DNA positive. There were no statistically significant differences in MCPyV prevalence according to age or gender. All specimens from nonmalignant chronic lung diseases and lung cancer were MCPyV negative. Conclusions: MCPyV was observed in specimens from patients with acute respiratory diseases, indicating that there may be a relationship between the virus and these diseases. We were not able to detect MCPyV in samples from patients with chronic lung diseases, including lung cancer, suggesting no association with MCPyV infection and no involvement of this polyomavirus in lung cancerogenesis.

History of chronic inflammatory disorders increases the risk of Merkel cell carcinoma, but does not correlate with Merkel cell polyomavirus infection

Background:We aimed to assess the connection between chronic inflammatory disorders (CIDs) and Merkel cell carcinoma (MCC).Methods: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.Results: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).Conclusions:Patients with CID are at significantly higher risk for aggressive MCC. Merkel cell polyomavirus positivity is more common in MCC patients unafflicted by CID.

A morphological and immunophenotypic map of the immune response in Merkel cell carcinoma

The susceptibility of Merkel cell carcinoma to the host immune response has prompted a search for effective immunotherapy. CD8-positive T lymphocytes are considered key effectors of this response, but the cellular infiltrates also harbor tumor-protective agents. By developing a comprehensive morphological and immunophenotypic map of tumor-infiltrating lymphocytes (TILS) in Merkel cell carcinoma, we aimed to establish a useful template for future studies. Twenty-two cases (mean age, 79years [range, 52-95]; male-female ratio, 10:12) were studied. TILS were categorized as brisk (7), nonbrisk (9), and absent(6). Merkel cell polyomavirus (MCPyV)-positive (16) and -negative (6) cases were included, as were those with pure (18) and combined (4) morphologies. One MCPyV+ case had undergone spontaneous regression. Immunohistochemical markers included CD3, CD4, CD8, CD20, CD68, FoxP3, PD-1, and CD123. Statistical analysis used Fisher exact tests and Spearman correlations. There was a significant correlation between brisk TILs and MCPyV+ status (P=.025). CD8+ T lymphocytes predominated, were present in significantly higher proportions in brisk infiltrates (P=.003), and showed a significant predilection for the intratumoral environment (P=.003). Immune inhibitors including T regulatory cells (FOXP3+) and PD-1+ "exhausted" immunocytes were present in lower proportions. Our findings support (1) the link between a brisk immune response and MCPyV positivity, (2) the supremacy of CD8+ cells in effecting immunity, and (3) the incorporation of immune inhibitors within the global infiltrate. Efforts to therapeutically arm the "effectors" and disarm the "detractors" are well focused. These will likely have the greatest impact on MCPyV-positive cases.

Correlation of Merkel cell polyomavirus positivity with PDGFRα mutations and survivin expression in Merkel cell carcinoma

BackgroundMerkel cell carcinoma (MCC) is a neuroendocrine cancer of the skin postulated to originate through Merkel cell polyomavirus (MCPyV) oncogenesis and/or by mutations in molecules implicated in the regulation of cell growth and survival. Despite the fact that MCPvV is detected more broadly within the population, only a part of the infected people also develop MCC. It is thus conceivable that together, virus and for example mutations, are necessary for disease development. However, apart from a correlation between MCPyV positivity or mutations and MCC development, less is known about the association of these factors with progressive disease. ObjectivesTo analyze MCPyV positivity, load and integration in MCC as well as presence of mutations in PDGFRα and TP53 genes and correlate these with clinical features and disease progression to identify features with prognostic value for clinical progression. MethodsThis is a study on a MCC population group of 64 patients. MCPyV positivity, load and integration in parallel to mutations in the PDGFRα and TP53 were analyzed on genomic DNA from MCC specimens. In addition, expression of PDGFRα, survivin and p53 proteins was analyzed by immunodetection in tissues specimens. All these parameters were analyzed as function of patient's disease progression status. Results83% of MCCs were positive for the MCPyV and among these 36% also displayed virus-T integration. Viral load ranged from 0.006 to 943 viral DNA copies/β-globin gene and was highest in patients with progressive disease. We detected more than one mutation within the PDGFRα gene and identified two new SNPs in 36% of MCC patients, whereas no mutations were found in TP53 gene. Survivin was expressed in 78% of specimens. We could not correlate either mutations in PDGFR or expression of PDGFR, p53 and surviving either to the disease progression or to the MCPyV positivity. ConclusionsIn conclusion, our data indicate that the viral positivity when associated with high viral load, correlates with poor disease outcome. Frequent mutations in the PDGFRα gene and high survivin expression were found in MCC independent of the viral positivity. These data suggest that these three factors independently contribute to Merkel cell carcinoma development and that only the viral load can be used as indicator of disease progression in virus positive patients.

Detection of Merkel cell polyomavirus large T-antigen sequences in human central nervous system tumors.

Despite decades of epidemiological investigation, little is known about the etiology of the central nervous system (CNS) tumors, and few well-established risk factors have been recognized. This study tested the presence of Merkel cell polyomavirus (MCPyV), the only member of the Polyomaviridae family convincingly linked to human cancer, in diverse CNS malignancies. In total, 58 CNS tumor biopsies were analyzed for the MCPyV large T-antigen (LT-Ag) gene by quantitative real-time PCR. Merkel cell polyomavirus LT-Ag DNA load was determined as viral copies per cell and viral copies per microliter of purified genomic DNA from CNS tumor samples. The MCPyV LT-Ag sequence was detected in 34 (58.6%) of the 58 tested samples. Viral LT-Ag was quantified in 19.0% of schwannomas, 13.8% of meningiomas, and 5.2% of pituitary adenomas. The difference between MCPyV positivity in different types of CNS malignancies was not statistically significant (P = 0.066). The mean LT-Ag copy number in 34 positive samples was 744.5 ± 737.7 and 0.056 × 10(-3) ± 0.091 × 10(-3) per microliter and per cell, respectively. Among MCPyV-positive CNS tumors, the mean MCPyV copy number was higher in meningiomas (993.8 ± 853.2 copy per microliter and 0.098 × 10(-3) ± 0.108 × 10(-3) copy per cell). Multiple linear regression analysis revealed statistically significant difference in MCPyV copy number between meningioma and other CNS tumor types, when the model was adjusted for age and sex (P = 0.024). This study shows the first evidence of the detection of MCPyV LT-Ag sequence at a low copy number in human CNS tumors.

Merkel cell Polyomavirus and p63 status in Merkel cell carcinoma by immunohistocnemistry: Merkel cell Polyomavirus positivity is inversely correlated with sun damage, but neither is correlated with outcome

The aim of this study was to determine the frequency of Merkel cell polyomavirus (MPyV) and p63 positivity by immunohistochemistry in a large cohort of primary Merkel cell carcinoma (MCC) from a region with high rates of actinic damage. We also aimed to determine whether there is any relationship between these markers and histological correlates of chronic sun exposure and to identify whether these markers have prognostic significance in our population. Ninety-five cases of primary cutaneous MCC were identified and stained with immunohistochemical markers for MPyV and p63. The presence of solar elastosis and squamous dysplasia in the overlying/adjacent skin were recorded as markers of actinic damage. Follow up data were obtained from the Western Australian Cancer Registry. MPyV was detected by immunohistochemistry in 23% of cases. There was a statistically significantly lower rate of positivity in tumours associated with markers of chronic sun damage as assessed by the presence of solar elastosis and squamous dysplasia. There was no association with overall or disease specific survival. p63 positivity was detected in 17% of cases. There was no association with markers of actinic damage or with overall or disease specific survival.Our data demonstrate a significant difference in rates of immunohistochemical positivity for MPyV between MCC in sun-damaged and non-sun-damaged sites. This may go some way to explaining previously identified geographical differences. When compared with a number of studies from Europe and North America, p63 positivity is less common in our population and does not show the strong prognostic significance that has been found in these other regions.

Usefulness of significant morphologic characteristics in distinguishing between Merkel cell polyomavirus–positive and Merkel cell polyomavirus–negative Merkel cell carcinomas

Merkel cell polyomavirus (MCPyV) monoclonally integrates into genomes of approximately 80% of Merkel cell carcinomas (MCCs) and undergoes mutation. We previously demonstrated statistically significant differences in tumor cell morphology and biology between MCPyV-positive and MCPyV-negative MCCs. We reassessed the usefulness of our morphologic criteria in differentiating MCPyV-negative and MCPyV-positive MCCs for practical diagnosis. Two trainees and 4 pathologists challenged estimations (5-point confidence scale) of MCPyV infection in MCCs using hematoxylin and eosin-stained slides of 43 new MCC cases and 2 morphologic criteria: (1) nuclear polymorphism is higher and cytoplasm is more abundant in MCPyV-negative MCC cells, and (2) MCC combined with squamous cell carcinoma is defined as MCPyV negative, regardless of tumor cell morphology of MCC. Subsequently, immunohistochemistry for MCPyV large T antigen and polymerase chain reaction for MCPyV DNA yielded concordant results (MCPyV positivity was 30/43 and 32/43, respectively) for 41 (96%) of 43 cases. The mean accuracy, sensitivity, and specificity of the trainees and pathologists were 92.4% ± 1.5% and 81.5% ± 11.0%, 95.6% ± 6.2% and 90.2% ± 8.3%, and 83.3% ± 11.8% and 74.6% ± 14.1%, respectively. Values of the areas under the curve were 0.80 to 0.95, indicating good informative scores. Using our morphologic criteria, observers can predict the absence of MCPyV infection and diagnose MCPyV-negative MCCs with poor prognosis. Unexpectedly, the performance of trainees was superior to that of pathologists, implying that our morphologic criteria are useful even for practitioners having little experience. Our morphologic criteria will provide pathologists with convenient and reliable hallmarks for accurate MCC diagnosis.

Lack of integrin β5 in Merkel cell carcinomas and derived cell lines is frequently associated with Merkel cell polyomavirus positivity

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin neoplasia. The Merkel cell polyomavirus (MCPyV), a double-stranded DNA tumour virus was discovered in 2008. It is found in approximately 80% of human MCC and is suspected to play a role in MCC development [1]. Both, small tumour and the aminoterminal moiety of the large tumour antigen, were found to be expressed in MCPyV-positive MCC [2]. Merkel cells are usually scattered in the basal cell layer of the epidermis along the dermo-epidermal junction [3].