Incidence trends of adult malignant brain tumors in Finland, 1990–2016

Background: Several studies have reported increased incidence trends of malignant gliomas in the late 1900s with a plateau in the 2000s, but also some recent increases have been reported. The purpose of our study was to analyze incidence trends of malignant gliomas in Finland by morphology and tumor location. Material and methods: Data on 4730 malignant glioma patients were obtained from case notifications to the nationwide, population-based Finnish Cancer Registry (FCR), and less detailed data on 3590 patients up to 2016. Age-standardized incidence rates (ASR) and average annual percent changes (APCs) in the incidence rates were calculated by histological subtype and tumor location. Results: The incidence rate of gliomas was 7.7/100,000 in 1990–2006 and 7.3 in 2007–2016. The incidence of all gliomas combined was stable during both study periods, with no departure from linearity. In an analysis by age group, increasing incidence was found only for ages 80 years and older (1990–2006). During both study periods, incidence rates were increasing in glioblastoma and decreasing in unspecified brain tumors. In 1990–2006, rates were also increasing for anaplastic oligodendroglioma, oligoastrocytoma and unspecified malignant glioma, while decreasing for astrocytoma. As for tumor location, incidence in 1990–2006 was increasing for frontal lobe and brainstem tumors, as well as those with an unspecified location, but decreasing for the parietal lobes, cerebrum and ventricles. Conclusions: No increasing incidence trend was observed for malignant gliomas overall. An increasing incidence trend of malignant gliomas was found in the oldest age group during 1990–2006.</p

Expression of iron-related genes in human brain and brain tumors

<p>Abstract</p> <p>Background</p> <p>Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (<it>HAMP</it>), HFE, neogenin (<it>NEO1</it>), transferrin receptor 1 (<it>TFRC</it>), transferrin receptor 2 (<it>TFR2</it>), and hemojuvelin (<it>HFE2</it>) in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines.</p> <p>Results</p> <p>Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens.</p> <p>Conclusion</p> <p>These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.</p

Lasten primaariset pahanlaatuiset aivokasvaimet : mitä olemme oppineet?

publishedVersionPeer reviewe

Complement activation in astrocytomas: deposition of C4d and patient outcome

Background C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. In this study C4d staining of grade I-IV astrocytic tumors was studied to explore if there is an association between complement activation and the grade of tumor, or patient survival. Methods Tissue micro-array samples of 102 astrocytomas were stained immunohistochemically. The material consisted of 9 pilocytic astrocytomas and 93 grade II-IV astrocytomas, of which 67 were primary resections and 26 recurrent tumors. The intensity of C4d staining as well as extent of C4d and CD34 staining were evaluated. The intensity of C4d staining was scored semiquantitatively. The extent of the staining was counted morphometrically with a point counting grid yielding a percent of C4d and CD34 positive area of the sample. Results The intensity and extent of C4d staining increased in grade II-IV diffusely infiltrating astrocytoma tumors in line with the malignancy grade (p = 0.034 and p = 0.016, respectively, Kruskal-Wallis test). However, C4d positive tumor area percentages were higher in grade I pilocytic astrocytomas than in grade II-IV diffusely infiltrating astrocytomas (p = 0.041, Mann–Whitney test). There was a significant correlation between CD34 positive and C4d positive endothelial area fraction in diffusely infiltrating astrocytomas (p < 0.001, Pearson correlation). In these tumors, the increasing intensity of C4d staining was also associated with worsened patient outcome (p = 0.014, log-rank test). Conclusion The worsening of patient outcome and malignant progression of tumor cells seem to be connected to microenvironmental changes evoked by chronically activated complement. Keywords: Astrocytoma; Glioblastoma; C4d; Complement; Inflammation; Survival;BioMed Central open acces

Pahanlaatuisuusaste ei yksin riitä - molekyylitutkimukset tarkentavat glioomien diagnostiikkaa

Vertaisarvioitu. Teema : aivokasvaimet. English summary.Glioomat ovat primaareista aivokasvaimista yleisimpiä. Glioomien diagnostiikka perustuu kasvainten histologisiin piirteisiin ja molekulaarisiin muutoksiin. Vuonna 2016 päivitetty WHO:n aivokasvainluokitus tuo geneettiset muutokset osaksi kasvainten diagnoosia. Integroitu diagnoosi sisältää kasvaimen histologisen tyypin, pahanlaatuisuusasteen ja molekulaariset muutokset. Glioomien tärkeimmät molekyylimuutokset ovat IDH (isositraattidehydrogenaasi) -geenin mutaatio ja 1p/19q-kodeleetio. Astrosytoomissa IDH-mutaatio erottaa suotuisan ennusteen kasvaimet omaksi ryhmäkseen. IDH-mutatoitumaton glioblastooma on glioomista tavallisin ja pahanlaatuisin. Paremman ennusteen oligodendroglioomassa on samanaikaisesti IDH-mutaatio ja 1p/19q-kodeleetio. H3 K27M -mutatoitunut keskiviivan gliooma on uusi aggressiivinen glioomatyyppi. Molekyylimuutoksiin perustuva luokittelu parantaa glioomien diagnostiikan tarkkuutta ja luo pohjan niiden tulokselliselle hoidolle.Peer reviewe

CLU, CR1 and PICALM genes associate with Alzheimer's-related senile plaques

Introduction APOE is the strongest risk gene for sporadic Alzheimer's disease (AD) so far. Recent genome wide association studies found links for sporadic AD with CLU and CR1 involved in Aβ clearance, and PICALM affecting intracellular trafficking. Methods We investigated the associations of senile plaques (SP) and neurofibrillary tangles (NFT) with the proposed risk genes and APOE, in the Tampere Autopsy Study (TASTY) series (603 cases), a sample of the general population (0 to 97 yrs), who died out-of-hospital. Results Age and the APOEε4 allele associated strongly with all phenotypes of SP, as expected. In age and APOEε4 adjusted analyses, compared to the most common homozygous genotype, burnt out SP were more common among carriers of the C-allele of CLU, whereas the T-allele of PICALM and C-allele of CR1 were linked with lower SP coverage. We found no significant associations between any of the genetic variants and NFT. Conclusions Marginal effects from CLU, CR1 and PICALM suggest that these genes have minimal effects on the development of AD lesions.BioMed Central Open acces

Diagnostically important muscle pathology in DNAJB6 mutated LGMD1D

Introduction: Limb girdle muscular dystrophies are a large group of both dominantly and recessively inherited muscle diseases. LGMD1D is caused by mutated DNAJB6 and the molecular pathogenesis is mediated by defective chaperonal function leading to impaired handling of misfolded proteins which normally would be degraded. Here we aim to clarify muscle pathology of LGMD1D in order to facilitate diagnostic accuracy. After following six Finnish LGMD1D families, we analysed 21 muscle biopsies obtained from 15 patients at different time points after the onset of symptoms. All biopsies were obtained from the lower limb muscles and processed for routine histochemistry, extensive immunohistochemistry and electron microscopy. Results: Histopathological findings were myopathic or dystrophic combined with rimmed vacuolar pathology, and small myofibrillar aggregates. These myofibrillar inclusions contained abnormal accumulation of a number of proteins such as myotilin, aB-crystallin and desmin on immunohistochemistry, and showed extensive myofibrillar disorganization with excess of Z-disk material on ultrastructure. Later in the disease process the rimmed vacuolar pathology dominated with rare cases of pronounced larger pleomorphic myofibrillar aggregates. The rimmed vacuoles were reactive for several markers of defect autophagy such as ubiquitin, TDP-43, p62 and SMI-31. Conclusions: Since DNAJB6 is known to interact with members of the chaperone assisted selective autophagy complex (CASA), including BAG3 - a known myofibrillar myopathy causing gene, the molecular muscle pathology is apparently mediated through impaired functions of CASA and possibly other complexes needed for the maintenance of the Z-disk and sarcomeric structures. The corresponding findings on histopathology offer clues for the diagnosis.Peer reviewe

Incidence trends of childhood central nervous system tumors in Finland 1990-2017

Introduction Central nervous system (CNS) tumors are a leading cause of cancer-related morbidity and mortality in children. Our aim is to characterize incidence trends of pediatric CNS tumors in Finland over the last three decades. Methods Data on all benign and malignant incident CNS tumors diagnosed in children aged 0-14 years in 1990-2017 were extracted from the Finnish Cancer Registry and classified according to the 2016 WHO classification of CNS tumors. We analyzed age-standardized incidence rates (ASR) for pediatric CNS tumors overall and by sex, age, tumor histology, grade, and location using Poisson regression. We used joinpoint regression to evaluate changes in trends. Results Overall, 1117 pediatric CNS tumor cases were registered in Finland with a 1.2:1 male to female ratio. The average annual ASR was 4.3 per 100,000 person-years (95% CI 4.26, 4.34). The most common tumor type was pilocytic astrocytoma (30% of tumors), followed by medulloblastoma (10%) with incidence rates of 1.30 and 0.45 per 100,000 person-years, respectively. The overall incidence of pediatric CNS tumors increased by an annual percentage change (APC) of 0.8% (95% CI 0.2, 1.4). We observed no major changes in incidence trends of tumor histology groups or tumor location groups. The ASR of benign tumors increased by an APC of 1.0 (95% CI 0.1, 2.0). Conclusions Utilizing the high-quality and completeness of data in the Finnish Cancer registry, we found that the incidence of pediatric CNS tumors in Finland has increased slightly from 1990 until 2017. Although variations in diagnostic and registration practices over time might have affected the rates, the trend may also reflect a true increase in incidence.Peer reviewe