MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies showed altered expression levels of several microRNAs in glioblastomas. In this study, we examined the expression levels of selected microRNAs in 22 primary glioblastomas and six specimens of adult brain tissue by real-time PCR method. In addition, we examined methylation status of MGMT promoter by methylation-specific real-time PCR, as this has been shown to be a predictive marker in glioblastomas. MGMT methylation status was not correlated with response to concomitant chemoradiotherapy with temozolomide (RT/TMZ). MiR-221 (p=0,016), miR-222 (p=0,038), miR-181b (p=0,036), miR-181c (p=0,043) and miR-128a (p=0,001) were significantly down-regulated in glioblastomas. The most significant change was observed for up-regulation in miR-21 expression in glioblastomas (p<0,001). MiR-181b and miR-181c were significantly down-regulated in patients who responded to RT/TMZ (p=0,016; p=0,047, respectively) in comparison to patients with progredient disease. Our data indicate for the first time that expression levels of miR-181b and miR-181c could serve as a predictive marker of response to RT/TMZ therapy in glioblastoma patients.

Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor; patients with GBM often have a very poor prognosis and differing responses to treatment. Therefore, it is very important to find new biomarkers that can predict clinical outcomes and help in treatment decisions. MicroRNAs are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and play a key role in the pathogenesis of GBM. In a group of 38 patients with primary GBM, we analyzed the expression of eight microRNAs (miR-21, miR-128a, miR-181c, miR-195, miR-196a, miR-196b, miR-221, and miR-222). In addition, we examined the methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter by high-resolution melting analysis, as this has been shown to be a predictive marker in GBM. MGMT methylation status correlated with progression-free survival (P = 0.0201; log-rank test) as well as with overall survival (P = 0.0054; log-rank test). MiR-195 (P = 0.0124; log-rank test) and miR-196b (P = 0.0492; log-rank test) positively correlated with overall survival. Evaluation of miR-181c in combination with miR-21 predicted time to progression within 6 months of diagnosis with 92% sensitivity and 81% specificity (P < 0.0001). Our data confirmed that the methylation status of MGMT but also miR-21, miR-181c, miR-195, and miR-196b to be associated with survival of GBM patients. Above all, we suggest that the combination of miR181c and miR-21 could be a very sensitive and specific test to identify patients at high risk of early progression after surgery. (Cancer Sci 2011; 102: 2186-2190 G lioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor of astrocytic origin.(1)Despite the introduction of modern therapeutic approaches, this cancer remains generally associated with very poor prognosis.(2) A significant benefit of overall survival (OS) has been achieved in patients treated with concomitant chemoradiotherapy with temozolomide (RT ⁄ TMZ), an alkylating agent. However, not all patients are sensitive to this therapy. (3,4) Because of an extremely short median survival time of glioblastoma patients and diversity in therapy response, it is very important to identify new biomarkers that can be used in prognosis and prediction of therapeutic response and ⁄ or clinical outcome in GBM patients in order to rationalize treatment decisions.MicroRNAs (miRNAs) are highly conserved, small, non-coding RNAs, 18-25 nucleotides in length, that function as posttranscriptional regulators of gene expression by silencing their mRNA targets. Bioinformatics tools estimate that miRNAs regulate up to one-third of human genes including a significant number of oncogenes, tumor suppressor genes, and genes associated with the invasion, dissemination, and chemoresistance of tumors.(5) Therefore, these molecules play significant roles in the pathogenesis of many cancers, including GBM. (6,7) In the context of this tumor, recent published reports have proposed that some miRNAs tha...

The role of nonclassical human leukocyte antigens G and E (HLA-G and HLA-E) was originally thought to be restricted to the protection of the fetus from a maternal allorecognition. Now it is known that HLA-G and HLA-E exert multiple immunoregulatory functions. A prognostic significance of the expression of HLA-G and HLA-E by neoplastic cells in glioblastoma is not well characterized. In this study, we evaluated the expression of HLA-G and HLA-E by neoplastic cells in 39 cases of glioblastoma. We found the production of HLA-G and HLA in a majority of cases. There was an unexpected positive correlation between the expression of HLA-E and length of survival. We speculate that the expression of this molecule by neoplastic cells may represent a coincidental selective pro-host advantage related to better response to subsequent therapeutic modalities. Mechanisms of glioblastoma cell pathophysiology and mechanisms of responses to therapeutic interventions in respect to the expression of these molecules deserves further study.

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ePLND comprised 83 % of SLNs, at least one SLN laid outside its template in 28 % of patients. ePLND and SLN dissection combined with nodal serial sectioning and immunohistochemistry increased the detection rate of nodal metastases by 68 % in comparison with ePLND alone and standard histology protocol.