Frequent detection of Merkel cell polyomavirus DNA in tissues from 10 consecutive autopsies.

Merkel cell polyomavirus (MCPyV) has been identified in samples of Merkel cell carcinoma (MCC), an aggressive skin cancer. Seroepidemiologic studies indicated a high frequency of MCPyV infection in humans, suggesting respiratory and faecal-oral routes, or transmission by skin contact. Since MCC is more frequent in immunocompromised patients, a reactivation of MCPyV latently infecting target cells has been proposed. However, neither definite ways of transmission nor specific target organs have been identified with certainty. Ten autopsies with an extensive organ sampling for a total of 121 specimens (tissue and blood samples) were collected. All tissue specimens were fixed in formalin and embedded in paraffin. Real-time PCR was performed to quantify the copy number of the large T antigen (LT) gene and the capsid VP1 gene of MCPyV. MCPyV LT and/or VP genes were detected in all of the collected specimens. A high prevalence of MCPyV was found in the blood (six cases) and lung (five cases); the brain was positive in three cases. The highest viral copy number was detected in blood from two autopsies (21 610 570.09 copies per 105 cells and 380 413.25 copies per 105 cells), whereas the viral copy number in the other organs was low. Our data confirm the high frequency of MCPyV infection in the general population, which seems to indicate that the respiratory tract is a possible route for viral transmission and viral persistence in the brain. The frequent detection of MCPyV DNA in blood suggests that circulating leukocytes could be one of the reservoirs of MCPyV, whereas the high viral copy number also seems to indicate the possibility of viral reactivation in immunocompetent adults.

Programmed cell death 1 ligand 1 (PD-L1) expression is associated with poor prognosis of malignant pleural mesothelioma patients with good performance status.

Malignant pleural mesothelioma (MPM) is often associated with a poor prognosis and options for the treatment of this disease are few. To date, the important role of the immune microenvironment in modifying the disease natural history is well established. The programmed cell death pathway (PD-1/PD-L1) limits the T lymphocyte activation in peripheral tissues when an inflammatory response occurs, and controls the tumour immune escape. PD-L1 is broadly expressed in several malignant tumours and associated with poor clinical outcomes. Thus, the aim of our study is to investigate the potential role of PD-L1 expression in MPM prognosis. Biopsy samples from 198 patients diagnosed with MPM were examined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate PD-L1 protein and gene expression. For PD-L1 protein expression we consider at least 5% membranous staining as positive. Gene expression levels were calculated with ΔΔCt method. Positive expression of PD-L1 by IHC was correlated with worse overall survival (OS; p=0.0225) in MPM patients. PD-L1 positive status was correlated with worse OS in the subgroup of patients with ECOG score <2 (p=0.0004, n=129) and these data were confirmed by multivariate analysis. No significant correlation was found between PD-L1 gene expression and OS. Our results show that PD-L1 evaluated by IHC assay may be a prognostic biomarker for MPM patients with good performance status.