Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin whose molecular pathogenesis is not completely understood, despite the role that Merkel cell polyomavirus can play in 55-90% of cases. To study potential mechanisms driving this disease in clinically characterized cases, we searched for somatic mutations using whole-exome sequencing, and extrapolated our findings to study functional biomarkers reporting on the activity of the mutated pathways. Confirming previous results, Merkel cell polyomavirus-negative tumors had higher mutational loads with UV signatures and more frequent mutations in TP53 and RB compared with their Merkel cell polyomavirus-positive counterparts. Despite important genetic differences, the two Merkel cell carcinoma etiologies both exhibited nuclear accumulation of oncogenic transcription factors such as NFAT or nuclear factor of activated T cells (NFAT), P-CREB, and P-STAT3, indicating commonly deregulated pathogenic mechanisms with the potential to serve as targets for therapy. A multivariable analysis identified phosphorylated CRE-binding protein as an independent survival factor with respect to clinical variables and Merkel cell polyomavirus status in our cohort of Merkel cell carcinoma patients.

Objective Cancer patients are at increased risk for psychological difficulties and COVID-19. We sought to analyze anxiety and depression levels during the COVID-19 pandemic and the association between sociodemographic, clinical, and psychological factors in patients with advanced cancer. Methods A prospective, multicenter cohort of 401 consecutive patients with newly diagnosed, advanced cancer completed the Brief Symptom Inventory, Michel Uncertainty in Illness Scale, Herth Hope Index, and Cancer Worry Scale between February 2020 and May 2021. Linear regression analyses explored the effects of uncertainty, hopelessness, and cancer worry on anxiety and depression, adjusting for sociodemographic and clinical variables. ResultsThe incidence of anxiety and depression was 36% and 35%, respectively. Emotional distress was greater among women, patients < 65 years of age, and those with an estimated survival of > 18 months. Linear regression analysis revealed that being female, preoccupation about cancer, and hopelessness were associated with increased levels of anxiety (p < 0.001) and depression (p < 0.001) and younger age was associated with a higher risk of anxiety. No differences in anxiety or depression levels were found in relation to marital status, children, educational level, cancer type, histology, stage, or type of treatment. Conclusions Patients with advanced cancer who initiated treatment during the pandemic experienced high levels of depression and anxiety. Early diagnosis and the development of intervention strategies are necessary, especially for specific patient subgroups, such as young women with long survival times.

No abstract

No abstract

No abstract