The predominant sites of viable and nonviable tumor were determined in the primary lesions of 50 patients with osteosarcoma after initial treatment with preoperative chemotherapy. The degree of tumor destruction was classified as good, fair, and poor and a map of the sites revealing viable and nonviable tumor was constructed. The study revealed several preferential sites where viable tumor was likely to persist: soft tissues, cortex, subcortex, ligaments, and areas in contact with cartilage (growth plate and/or articular cartilage). Localized areas of hemorrhage and necrosis, designated "lacunae," were noted within the tumor. They were frequently surrounded by bundles of viable tumor and appeared to correlate with open surgical biopsies. Factors responsible for this phenomenon and the persistence of viable tumor are discussed. The findings have important implications in the design of surgical treatment and in the use of needle biopsies to determine the effects of preoperative treatment.

Thirty-three chordomas were observed at the Istituto Nazionale Tumori of Milan from 1933 to 1983: 27 sacrococcygeal, 3 spheno-occipital, and 3 vertebral. The male:female ratio was 2.7, and the median age was 63 yr for patients with sacrococcygeal and 35.2 yr for those with nonsacral chordomas. After pathologic reassessment, distinct cytologic patterns were found: physaliphorous, syncytial, and mixed subtypes, with variable degrees of cytologic atypia. However, no evident difference in survival was documented in relation to these cytohistologic features. Four cases had a prior traumatic fracture, and the pathogenetic role of trauma is stressed. Eight cases were operated with adequate surgery and only three recurred, whereas of 11 inadequate operations, 10 developed local relapse. However, follow-up for recent adequate operations is short. Radiation therapy seemed to be effective with adjuvant or palliative aims. No chemotherapeutic regimen achieved any result; one case had a short complete remission after cis-dichlorodiammineplatinum + vinblastine + bleomycin (PVB). This analysis confirms the possibility of achieving radicality with high resection of the sacrum for lesions confined below the second sacral vertebra. Nonsacral chordomas were all unresectable. The best treatment for unresectable lesions seems to be palliative surgery plus radiotherapy.

The clinicopathological features of a series of neuronal and mixed neuronal and astrocytic neoplasms of the CNS are described. Patients were aged 5 to 63 years. Six cases were composed predominantly of small round cells with clear cytoplasm resembling central neurocytoma but lacked the characteristic intraventricular location of that tumor. The remaining five cases had similar neurocytomatous features associated with a benign astrocytic component. Ganglion cells and hyalinization vessels were observed in both groups. The growth fraction evaluated with monoclonal antibody Ki67Mib1 was low, ranging from 1 to 1.5%. Immunohistochemical detection of synaptophysin played a crucial role in identifying the neuronal nature of these neoplasms and was instrumental in distinguishing them from oligodendrogliomas, with which they are readily confused. The neuronal nature of the oligodendroglial-like cells was confirmed ultrastructurally in one case. The present cases, together with others reported previously, suggest that neoplasms of the CNS with "neurocytic" components are more frequent than generally assumed and expand the morphologic spectrum of neuronal and mixed neuronal-glial tumors. Except for one patient who died postoperatively, all patients were alive at follow-up ranging from 6 to 80 months.

Microvessel density (MVD) is considered to be a prognostic marker in many tumours. Nevertheless, conflicting results were achieved regarding its prognostic role in meningiomas when it was quantified through pan-endothelial markers such as CD34, CD31 or Factor VIII. In the present study, MVD was assessed in meningiomas through the specific marker for neo-angiogenesis CD105. Fifty-four formalin fixed, paraffin embedded, surgical cases of meningiomas (WHO 28 grade I and 26 grade II) as well as ten normal leptomeningeal samples were submitted to immunohistochemical analysis for CD105. CD34 immuno-expression was also evaluated on consecutive parallel sections. For each case, MVD was estimated in terms of number of vessels/mm(2). CD105 was not evidenced in normal samples, whereas it was demonstrated in the vessels within 14/28 WHO grade I cases and within 24/26 WHO grade II meningiomas. On the contrary, CD34 antibody stained blood vessels in both normal and neoplastic samples; moreover, in each case, it stained more microvessels than CD105 antibody (25.33 +/- 21.16 vs. 50.72 +/- 26.75). Higher CD105 counts were significantly correlated with higher histological grade and Ki-67 LI > 4%. No statistical significant correlations were encountered between MVD measured by either CD105 and CD34 and sex, age, site of tumour or extent of surgical resection. CD105-MVD, but not CD34-MVD, showed an inverse significant correlation with overall survival and recurrence-free survival. In conclusion, our study suggests the higher specificity of CD105 in comparison to pan-endothelial markers in the evaluation of meningioma neo-angiogenesis, and its higher prognostic significance. CD105 might serve as a target for therapeutic approaches blocking blood supply in meningiomas.

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.

Despite advances in the treatment of glioblastoma (GBM), median survival is 12-15 months. O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation status is acknowledged as a predictive marker for temozolomide (TMZ) treatment. When MGMT promoter values fall into a "methylated" range, a better response to chemotherapy is expected. However, a cutoff that discriminates between "methylated" and "unmethylated" status has yet to be defined. We aimed to identify the best cutoff value and to find out whether variability in methylation profiles influences the predictive capacity of MGMT promoter methylation. Data from 105 GBM patients treated between 2008 and 2013 were analyzed. MGMT promoter methylation status was determined by analyzing 10 CpG islands by pyrosequencing. Patients were treated with radiotherapy followed by TMZ. MGMT promoter methylation status was classified into unmethylated 0-9 %, methylated 10-29 % and methylated 30-100 %. Statistical analysis showed that an assumed methylation cutoff of 9 % led to an overestimation of responders. All patients in the 10-29 % methylation group relapsed before the 18-month evaluation. Patients with a methylation status ≥30 % showed a median overall survival of 25.2 months compared to 15.2 months in all other patients, confirming this value as the best methylation cutoff. Despite wide variability among individual profiles, single CpG island analysis did not reveal any correlation between single CpG island methylation values and relapse or death. Specific CpG island methylation status did not influence the predictive value of MGMT. The predictive role of MGMT promoter methylation was maintained only with a cutoff value ≥30 %.

Interest is increasing in biological scaffolds for tissue regeneration, such as extracellular matrix (ECM) membranes, developed through soft tissue decellularization. The present study describes the development of a chemicophysical decellularization method applied to allogenic human-derived dermis (HDM). To evaluate the absence of viable cells and the maintenance of ECM structure, biological, histological and ultrastructural assessments were performed on the HDM membrane. Residual DNA content and glycosaminoglycan (GAG) and collagen contents were quantified. Growth factor (GF) release was directly measured on HDM extracts and indirectly measured by assessing cell proliferation after administering extract to cultures. Tensile tests were performed to measure the effect of the decellularization technique on the mechanical properties of tissue. Histocompatibility was investigated after subcutaneous implantation in rats. Residual DNA, GAG and collagen content measurements, vitality index, histology and electron microscopy showed the efficiency of the decellularization process and preservation of ECM matrix and bioactivity. In HDM extracts, among the tested GFs, transforming growth factor-β1 showed the highest concentration. HDM extracts significantly increased the proliferation rate of L929 fibroblasts in comparison with controls (p < 0.005, p < 0.05 and p < 0.0005). Maximum load and stiffness of HDM were significantly higher than those of cellularized dermis (p < 0.0005, p < 0.005). Histological and histomorphometric analysis of explanted samples showed that the membrane was integrated with host tissues in the absence of inflammatory reactions. Our results show that the decellularization method allowed the development of a human allograft dermal matrix that might be useful for soft tissue regeneration.

Caveolin-1 (Cav-1) protein has been documented in several neoplasms with a controversial role in cell proliferation, tumour development and progression. The aim of the present study was to investigate the Cav-1 immunohistochemical expression in human meningiomas. Sixty-two cases, classified as 11 meningothelial (17%), 12 transitional (19%), 5 fibrous (8%), 3 microcystic (5%), 3 secretory (5%), 1 clear cell (2%), 1 chordoid (2%) and 26 (42%) atypical meningiomas, were selected from our pathological files. Clinico-pathological data, including Ki-67 values and survival data were also available. Ten leptomeningeal samples were utilized as normal tissue control. For each case, a polyclonal antibody against Cav-1 was applied and an intensity distribution (ID) score was determined. The Cav-1 immunoexpression was found in 95% of meningiomas with a variable ID score, while only minimal, not uniform, reactivity was noted in non-neoplastic meninges. Of note, higher Cav-1 ID score was significantly correlated with tumour site, Simpson's grade, histological type, higher histologic grade, Ki-67 labelling index > or = 4% and clinical course. Kaplan-Meier curves demonstrated a significantly worse survival in patients with higher Cav-1 ID score, Ki-67 > or = 4% and 2-3 Simpson grade. Multivariate analysis indicated that only Ki-67 was an independent prognostic factor. Increased immunoexpression of the Cav-1 seems to be associated with the biological aggressiveness of meningiomas, reflecting a worse prognosis.