Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

Usefulness of immunological detection of the human telomerase reverse transcriptase 353 histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections,

Abstract. Objective: Recent years have seen a considerable wealth of studies conducted on the potential usefulness of telomerase determination in diagnosis, prognosis and targeted cancer therapy. The frequently used Telomeric Repeat Amplification Protocol assay suffers from some drawbacks, the most important being the rate of false positives. In situ analysis using well characterised antibodies directed against the human telomerase reverse transcriptase (hTERT) would therefore appear to be important to morphologically identify the nature of telomerase positive cells. Methods: We performed immunostaining in a series of cultured cells and in normal, preneoplastic and tumour tissues from different organs using a monoclonal antibody directed against the catalytic subunit of telomerase. Results: Immunoreactivity was not observed in perennial cells of terminally differentiated cardiac and skeletal muscular tissues or in small pyramidal cells of the cerebral cortex. Conversely, it was found in other normal somatic tissues as well as in precancerous lesions and in all tumour histotypes. Conclusions: Immunohistochemistry with a well characterised hTERT-specific monoclonal antibody permitted the identification of hTERT immunopositive cells in normal somatic tissues. Whether hTERT protein detected by immunostaining with hTERT-specific Tel 3 36-10 antibody is actually the degraded form of the protein that retains hTERT antigenicity but not enzymatic function, or whether it represents the real, potentially functional catalytic subunit of the enzyme, immunohistochemistry would not seem to represent a useful tool to investigate the role of telomerase and the mechanisms involved in its regulation

Nonrandom gain of chromosome 7 in central neurocytoma: A chromosomal analysis and fluorescence in situ hybridization study

Central neurocytoma is a benign, slow-growing neoplasm with favourable prognosis. Biomolecular analysis has failed to demonstrate significant alterations, and no cytogenetic alterations have been reported. In this study we demonstrate chromosome 7 gain in three of nine neurocytomas (33%). Traditional cytogenetic analysis performed in four of the nine cases identified trisomy 7 as the sole chromosomal abnormality in one case. In terphase cytogenetics utilizing fluorescent in situ hybridization (FISH) on cell suspensions from formalin-fixed paraffin-embedded tumour tissue performed in all nine cases detected trisomy 7 in two more cases and tetrasomy in another. Our results suggest that chromosome 7 gain is a feature of neuroectodermal tumorigenesis, possibly conferring growth advantage on the neoplastic cells. FISH on interphase nuclei is a valuable adjunct in the genetic evaluation of rare central nervous system neoplasms with low baseline proliferative activity

Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I\u2013III

Several biomarkers have been proposed as useful parameters to better specify the prognosis or to delineate new target therapy strategies for glioblastoma patients. MicroRNAs could represent putative target molecules, considering their role in tumorigenesis, cancer progression and their specific tissue expression. Although several studies have tried to identify microRNA signature for glioblastoma, a microRNA profile is still far from being well-defined.In this work the expression of 19 microRNAs (miR-7, miR-9, miR-9*, miR-10a, miR-10b, miR-17, miR-20a, miR-21, miR-26a, miR-27a, miR-31, miR-34a, miR-101, miR-137, miR-182, miR-221, miR-222, miR-330, miR-519d) was evaluated in sixty formalin-fixed and paraffin-embedded glioblastoma samples using a locked nucleic acid real-time PCR. Moreover, a comparison of miRNA expressions was performed between primary brain neoplasias of different grades (grades IV-I).The analysis of 14 validated miRNA expression in the 60 glioblastomas, using three different non-neoplastic references as controls, revealed a putative miRNA signature: mir-10b and miR-21 were up-regulated, while miR-7, miR-31, miR-101, miR-137, miR-222 and miR-330 were down-regulated in glioblastomas. Comparing miRNA expression between glioblastoma group and gliomas of grades I-III, 3 miRNAs (miR-10b, mir-34a and miR-101) showed different regulation statuses between high-grade and low-grade tumors. miR-10b was up-regulated in high grade and significantly down-regulated in low-grade gliomas, suggesting that could be a candidate for a GBM target therapy.This study provides further data for the identification of a miRNA profile for glioblastoma and suggests that different-grade neoplasia could be characterized by different expression of specific miRNAs

Name, chromosomal localization and expression level in GBM according to previously described data of miRNAs analysed in this study.

<p>Name, chromosomal localization and expression level in GBM according to previously described data of miRNAs analysed in this study.</p

Scatter plot showing Spearman correlation between Fresh/Frozen and FFPE-dissected groups.

<p>Scatter plot showing Spearman correlation between Fresh/Frozen and FFPE-dissected groups.</p

Median fold-change calculated per each miRNA between 30 paired Fresh/Frozen and FFPE samples.

<p>The y-axis represents the fold-change value.</p