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

Glioomien diagnoosi ja ennuste - molekyylidiagnostiikan mahdollisuudet

Glioomat ovat aivojen tukisolukasvaimia ja primaarisista aivokasvaimista yleisimpiä. Diffuusien glioomien hoito perustuu kasvaimen kirurgiseen poistoon sekä säde- ja solunsalpaajahoitoon. Diagnoosi tehdään kasvaimen histopatologisesta tutkimuksesta, jota voidaan nykyisin täydentää molekyylidiagnostisilla tutkimuksilla. Esitämme Tampereen yliopistollisessa sairaalassa vuosina 1983-2009 hoidettujen glioomapotilaiden ennustetta kuvaavia uusia menetelmiä, joista tärkeimpiä ovat IDH-mutaation ja 1p/19q-kodeleetion osoitukset. Tulevaisuudessa voi olla mahdollista räätälöidä hoitoa potilaskohtaisesti glioomien profiloinnin perusteella

Impact of Timing of Surgery and Adjuvant Treatment on Survival of Adult IDH–wild-type Glioblastoma : A Single-center Study of 392 Patients

Background: The purpose of our study was to analyze the impact of time interval from referral to surgery and from surgery to adjuvant treatment on survival of adult isocitrate dehydrogenase–wild-type (IDH-wt) glioblastomas. Methods: Data on 392 IDH-wt glioblastomas diagnosed at the Tampere University Hospital in 2004–2016 were obtained from the electronic patient record system. Piecewise Cox regression was used to calculate hazard ratios for different time intervals between referral and surgery, as well as between surgery and adjuvant treatments. Results: The median survival time from primary surgery was 9.5 months (interquartile range: 3.8–16.0). Survival among patients with an interval exceeding 4 weeks from referral to surgery was no worse compared to <2 weeks (hazard ratio: 0.78, 95% confidence interval: 0.54–1.14). We found indications of poorer outcome when the interval from surgery to radiotherapy exceeded 30 days (hazard ratio: 1.42, 95% confidence interval: 0.91–2.21 for 31–44 days; and 1.59, 0.94–2.67 for over 45 days). Conclusions: Interval from referral to surgery in the range of 4–10 weeks was not associated with decreased survivals in IDH-wt glioblastomas. In contrast, delay exceeding 30 days from surgery to adjuvant treatment may decrease long-term survival.Peer reviewe

PTPRD and CNTNAP2 as markers of tumor aggressiveness in oligodendrogliomas

Oligodendrogliomas are typically associated with the most favorable prognosis among diffuse gliomas. However, many of the tumors progress, eventually leading to patient death. To characterize the changes associated with oligodendroglioma recurrence and progression, we analyzed two recurrent oligodendroglioma tumors upon diagnosis and after tumor relapse based on whole-genome and RNA sequencing. Relapsed tumors were diagnosed as glioblastomas with an oligodendroglioma component before the World Health Organization classification update in 2016. Both patients died within 12 months after relapse. One patient carried an inactivating POLE mutation leading to a clearly hypermutated progressed tumor. Strikingly, both relapsed tumors carried focal chromosomal rearrangements in PTPRD and CNTNAP2 genes with associated decreased gene expression. TP53 mutation was also detected in both patients after tumor relapse. In The Cancer Genome Atlas (TCGA) diffuse glioma cohort, PTPRD and CNTNAP2 expression decreased by tumor grade in oligodendrogliomas and PTPRD expression also in IDH-mutant astrocytomas. Low expression of the genes was associated with poor overall survival. Our analysis provides information about aggressive oligodendrogliomas with worse prognosis and suggests that PTPRD and CNTNAP2 expression could represent an informative marker for their stratification.publishedVersionPeer reviewe

Glioomien diagnoosi ja ennuste - molekyylidiagnostiikan mahdollisuudet

Glioomat ovat aivojen tukisolukasvaimia ja primaarisista aivokasvaimista yleisimpiä. Diffuusien glioomien hoito perustuu kasvaimen kirurgiseen poistoon sekä säde- ja solunsalpaajahoitoon. Diagnoosi tehdään kasvaimen histopatologisesta tutkimuksesta, jota voidaan nykyisin täydentää molekyylidiagnostisilla tutkimuksilla. Esitämme Tampereen yliopistollisessa sairaalassa vuosina 1983-2009 hoidettujen glioomapotilaiden ennustetta kuvaavia uusia menetelmiä, joista tärkeimpiä ovat IDH-mutaation ja 1p/19q-kodeleetion osoitukset. Tulevaisuudessa voi olla mahdollista räätälöidä hoitoa potilaskohtaisesti glioomien profiloinnin perusteella

Chronic subdural hematoma : incidence, complications, and financial impact

publishedVersionPeer reviewe