Aberrant expression of ALK and EZH2 in Merkel cell carcinoma

BACKGROUND: Distinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. Many mutational studies on MCC have been carried out in recent years without identifying a prominent driver mutation. However, there is paucity reporting the expression of cancer genes at the RNA level in MCC tumors. In this study, we studied the RNA expression profiles of 26 MCC tumors, with a goal to identify prospective molecular targets that could improve the treatment strategies of MCC. METHODS: RNA expression of 50 cancer-related genes in 26 MCC tumors was analyzed by targeted amplicon based next-generation sequencing using the Ion Torrent technology and the expression compared with that of normal, non-cancerous skin samples. Sequencing data were processed using Torrent Suite Software. Expression profiles of MCV-negative and MCV-positive tumors were compared. Fluorescence in situ hybridization was performed to study ALK rearrangements and immunohistochemistry to study ALK expression in tumor tissue. RESULTS: ALK, CDKN2A, EZH2 and ERBB4 were overexpressed, and EGFR, ERBB2, PDGFRA and FGFR1 were underexpressed in MCC tumors compared to normal skin. In the MCV-negative tumors, MET, NOTCH1, FGFR3, and SMO were overexpressed and JAK3 and NPM1 were under-expressed compared to the MCV-positive tumors. CONCLUSIONS: High expression of ALK, CDKN2A and EZH2 was recorded in MCC tumors. No ALK fusion was seen by FISH analysis. Overexpression of EZH2 suggests its potential as a drug target in MCC.Peer reviewe

Symptom burden in community-dwelling older people : temporal trends in the Helsinki Aging Study

Background Changes in older people's symptoms across recent decades have not been investigated. Aims We analyzed temporal trends in symptom burden by comparing data from independent, cross-sectional cohorts retrieved in 1989, 1999, 2009, and 2019. Furthermore, we compared the association between symptom burden and psychological wellbeing (PWB) in older men and women. Methods The Helsinki Aging Study recruited a random sample of people aged 75, 80, and 85 in 1989, and random samples aged 75, 80, 85, 90, and 95 in 1999, 2009, and 2019 (four study waves). Altogether, 6263 community-dwelling people answered the questions concerning symptoms in the questionnaire surveys. The symptoms inquired in all study waves were dizziness, back pain, joint pain, chest pain, shortness of breath, and loss of appetite. Symptom burden was calculated according to the number of symptoms and their frequency (score range: 0-6). PWB and the Charlson comorbidity index were calculated. Results Symptom burden decreased in both men and women aged 75 and 80 from 1989 to 2019. Changes in cohorts aged 85 + were nonsignificant. There was a significant difference in symptom burden between men and women in all ages with men having fewer symptoms. PWB decreased with increasing symptom burden. Men had greater PWB than women up to severe levels of symptom burden. Conclusions Symptom burden decreased from 1989 to 2019 in cohorts aged 75-80, whereas changes remained nonsignificant in cohorts aged 85 +. To our knowledge, this is the first study to examine temporal trends in symptom burden.Peer reviewe

Symptom Burden Is Associated with Psychological Wellbeing and Mortality in Older Adults

Importance Over half of outpatient visits are due to physical symptoms; yet, the significance of symptoms in relation to older people's wellbeing and prognosis has gained very little research attention. Objectives This study aims to analyze the prognostic value of symptom burden, derived from symptom count and frequency, in an older cohort aged 75 to 95. We also explore the association between symptom burden and psychological wellbeing. Design Randomly assigned cohorts of community-dwelling people aged 75-95 filled in the postal questionnaire of the Helsinki Aging Study in 2009. Setting Community-based, postal questionnaires (survey response rate 74%). Participants 1583 community-dwelling people aged 75-95 in the urban Helsinki area. Main outcomes and measures The inquired symptoms were dizziness, back pain, joint pain, chest pain or discomfort, shortness of breath, leg pain when walking, loss of appetite, and urinary incontinence. Symptom burden was calculated according to the number of symptoms and their frequency (score range: 0-8). The participants were subdivided into four groups according to their symptom burden. Mortality data was extracted from the Finnish Population Register in 2014. Psychological wellbeing (PWB) was measured using the validated PWB score. Results Of 1583 participants, 18% reported no symptoms over the past 2 weeks (Group 0), 31% scored 0.5-1 in the symptom burden score (Group 1), 23% scored 1.5-2 (Group 2), and 28% scored 2.5-8 (Group 3). There was a linear relationship between symptom burden and comorbidities, functional status, falls, and PWB. The groups showed a significant difference in 5-year mortality, even adjusted for age, sex, and comorbidities: Group 1 1.18, 95% CI 0.84-1.66; Group 2 1.63, 95% CI 1.15-2.31, and Group 3 2.08, 95% CI 1.49-2.91 compared to Group 0 (p for linearityPeer reviewe