ABSTRACT
Gliomas are the most common primary brain tumors. Despite therapeutic advances, the majority of gliomas do not respond to either chemo or radiotherapy. CD117, the gene product of c-kit has been expressed in glial tumors. Because gastrointestinal stromal tumors [GISTs] that express CD117 respond dramatically to treatment with tyrosine kinase inhibitors, identification of glial tumors that express CD117 might open new therapeutic approaches for treatment of these tumors. This work was planned to study the role of CD117 [KIT] in the development and progression of gliomas mainly astrocytomas. Also, to assess if CD117 might serve as a biomarker for those gliomas that might respond to tyrosine kinase inhibitors. We studied 71 cases of gliomas. They were 59 astrocytomas, 9 ependymomas, 2 mixed oligoastrocytomas and single case of anaplastic oligodendroglioma. Paraffin embedded sections were immunostained using primary antibodies against CD117. Antigen antibody reaction was detected by streptavidin-biotin kit. In the present work, CD 117 immunoreactivity was noted in different grades of astrocytomas. The CD 117 average weighted scores showed gradual upregulation with increasing grade from pilocytic astrocytoma [16.7%]-diffuse astrocytoma grade II [33.3%]-anaplaslic astrocytoma [66.7%]-glioblastoma multiforme [79.3%.]. Majority of the gliomas [57.7%.] were found to express CD117 to varying degrees, and high grade tumors [78.6%] had a higher proportion of CD117 expression than low grade tumors [27.6%]. In 21.12% of studied cases, the CD117 was expressed in endothelial cells of tumor blood vessels. Twelve cases of them [80%] were most prominent in microvascular proliferations of high grade tumors and eleven cases of them showed strong intensity. High grade astrocytomas [especially glioblastoma multiforme] showed more frequent and strong expression of CD117, this indicate that CD]117 may has possible role in early astrocytoma tumorigenesis and in progression. Also, CD117 may serve as a biomarker for those gliomas that respond to tyrosine kinase inhibitor drugs
Subject(s)
Humans , Male , Female , Proto-Oncogene Proteins c-kit , BiomarkersABSTRACT
Alteration of the P53 tumor suppressor gene is implicated in tumorigenesis and in progression of a wide variety of human cancers, including gliomas. Accumulation of P53 protein is used as indicator of alteration in P53 gene. Less is known about P53 expression in reactive non-neoplastic lesions [gliosis]. This work is done to verify, the presence of P53 in astrocytomas through immunohistochemistry as well as correlating its expression with clinicopathological parameters and to detect its role in differentiating gliosis from low grade astrocytomas. Ninety-one astrocyromas and 24 cases of reactive gliosis were retrospectively collected from Pathology Department in Assiut University Hospital and private laboratories. Astrocytomas were classified and graded according to WHO classification [2000] using H and E stained sections from formalin fixed paraffin embedded blocks. P53 was immunohistochemically evaluated in selected 46 cases of astrocytomas and 12 cases of reactive gliosis. Glioblastoma multiforme [WHO grade IV] was the predominant grade of astrocytomas. The mean age of patients with asirocytomas showed upregulation with grade. There was male sex predilection in all grades of astrocytomas. P53 protein was detected in 58.7% of astrocytomas including all grades. The immunoreactivity score showed gradual upregulation with increasing grade. There was positive insignificant correlation between P53 expression and age, cellularity and mitosis and positive significant correlation between its expression and pleomorphism, microvascular proliferation and necrosis. All cases of ghosts except one showed negative P53 immunoreactivity. In P53 protein alteration is an early event in lumarigenesis and progression of astrocytomas and is a useful diagnostic tool in diagnosis of high grade gliomas. P53 provides just one more procedure in differentiation of glios is from low grade astrocyromas