Glioblastoma multiforme (GBM), a highly aggressive brain cancer characterized by uncontrolled proliferation, resistance to cell death, angiogenesis, and vascular edema, remains one of the deadliest types of cancer. The subventricular zone (SVZ) harbors cells with great proliferative potential, and the microenvironment within the SVZ is permissive to growth and proliferation. This neurogenic niche is suspected to be a vulnerable site for the origin of subtypes of GBM. The aim of our study was to determine the immunohistochemical expression of mIDH1 and YKL40 in relationship to the SVZ of GBMs. YKL40, also known as chitinase-like protein 1, is included as a mesenchymal marker and associated with a poor prognosis. The protein is a secreted inflammatory molecule with no chitinolytic activity. However, the mutation of IDH1 (mIDH1) has been found in the cytoplasm and peroxisomes of 70-80% of secondary GBMs. In our study we found that YKL40-positive GBM is significantly linked to SVZ types IV and V (p < 0.0001). Our results show the diversity among GBMs related to the SVZ, which should be considered in the design of future targeted therapies. There was a significant impact of patient age, mIDH1 positivity, SVZ type III, and chemoradiotherapy on overall survival.

Given the involvement of HSPGs in AD pathology, there would seem to be a relationship between the regulation of heparanase expression, the features of the disease, and a possible therapeutic alternative.

Chordomas are rare and low-grade malignant solid tumours, despite their histologically benign appearance, that arise in the bone from embryonic notochordal vestiges of the axial skeleton, a mesoderm-derived structure that is involved in the process of neurulation and embryonic development. Chordomas occurring in the skull base tend to arise in the basiocciput along the clivus. Three major morphological variants have been described (classical, chondroid, and atypical/dedifferentiated). The pathogenesis and molecular mechanisms involved in chordoma development remain uncertain. From a pathological standpoint, the microenvironment of a chordoma is heterogeneous, showing a dual epithelial-mesenchymal differentiation. These tumours are characterised by slow modality of biologic growth, local recurrence, low incidence of metastasis rates, and cancer stem cell (CSC) phenotype. The main molecular findings are connected with brachyury immunoexpression and activation of the downstream Akt and mTOR signalling pathways. The differentiation between typical and atypical chordomas is relevant because the tumoural microenvironment and prognosis are partially different. This review provides an insight into the recent and relevant concepts and histochemical markers expressed in chordomas, with special emphasis on dedifferentiated chordomas and their prognostic implications.

A b s t r a c t

No abstract