Prognostic Significance of Immunohistochemical Markers in Glioma Patients

Gliomas are the most common form of brain tumors, contributing to more than half of the incidence of brain tumors. They are derived from three basic types of glial cells: astrocytes, oligodendrocytes and ependymal cells. The most frequent are diffusely infiltrating astrocytomas, further classified into astroytomas (A), anaplastic astrocytomas (AA) and glioblastoma, equivalent to World Health Organization (WHO) grade II, II and IV, respectively (Kleihues & Cavenee, 2000). The term glioblastoma is used synonymously with glioblastoma multiforme (GBM), which suggests, the histopathology of this tumor is extremely variable (Kleihues & Cavenee, 2000). GBM is the most common and lethal type of astrocyte-derived tumor, corresponding to 50% of adult primary brain tumor cases, followed by anaplastic astrocytoma (30%) and astrocytoma (20%) (Greenberg, 2010). GBM may develop from astrocytoma or anaplastic astrocytoma (secondary GBM), but more frequently they manifest after a short clinical history de novo, without any evidence of a less malignant precursor lesion (primary GBM) (Farhadi & Rutka, 2008). Although primary brain tumors are relatively rare compared with carcinomas, they are characterized by higher mortality rates and increased disability. The overall annual incidence rate of primary malignant and benign brain tumors in developed countries is approximately 15 per 100,000 individuals, and for primary malignant brain tumors it is 7 per 100,000 (Minn et al., 2008). Brain tumor incidence and mortality have increased by up to 300% over the past 3 decades primarily in people aged over 75 years (Davis et al., 1996 as cited in Minn et al., 2008; Wrensch et al, 1993 as cited in Minn et al., 2008). Malignant gliomas are among the most challenging of all cancers to treat successfully. The tumor cells vigorously invade surrounding tissue, which renders complete surgical resection difficult and contributes to the high incidence of the recurrence (Merzak et al., 1995). Invasion of glioma cells into adjacent brain tissue is dependent on their interaction with the extracellular matrix (ECM) and possible destruction of matrix barriers (Pilkington, 1994). Tumor cells at the invasive front have to detach from the primary tumor mass and reattach to ECM components or to surrounding tissue elements. In general, invasiveness may result in deformation and destruction of the brain architecture which leads to the fatal outcome for the patient. Proteolytic modification of ECM components, such as laminin and