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Abstract

The expression of two novel proliferation-associated markers, mitosin and topoisomerase II␣ (Topo II␣), was evaluated immunohistochemically in consecutive paraffin sections from 60 diffuse astrocytomas (grades 2 to 4) in relation to clinicopathologic parameters, proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1) expression and survival. The percentage of mitosin and Topo II␣-positive cells (LI) increased with grade and Ki-67 LI, but could not discriminate between grade 3 on the one hand and grades 2 or 4 on the other hand. In 51% of cases, Ki-67 LI exceeded Topo II␣ LI, especially within grade 4. Topo II␣ and mitosin expression was adversely related to overall and disease-free survival in the entire cohort and in grades 2/3. However, only Topo II␣ LI affected disease-free survival in grade 4 tumors. Multivariate analysis selected only mitosin LI along with the age of the patient, as the independent parameters predicting overall survival, whereas Topo II␣ emerged as the single independent predictor of disease-free survival. It is concluded that the proliferative potential of astrocytomas, as measured by mitosin and Topo II␣ immunostaining, conveys useful prognostic information, in addition to that obtained by standard clinicopathologic parameters.

Gene Expression Profiling of Hypothalamic Hamartomas: A Search for Genes Associated with Central Precocious Puberty

“…This analysis indicated that the genes overexpressed in HH-1 encode proteins involved in three fundamental cellular processes: transcriptional regulation, cell-cell communication and cell adhesiveness (table 3). With the possible exception of CENP-F (mitosin), a cell cycle-regulated nuclear protein [9] found at very low levels in the normal brain (http://source.stanford.edu), but that is overexpressed in malignant tissues, including astrocytomas and meningiomas [[10] and references therein], all other genes are highly expressed in the normal developing brain in either neurons, astrocytes or both (table 3). …”

“…One of them is CENP-F [10]. Two others, IA-1 (insulinoma-associated-1, also known as INSM1 ) and MEF2A , are transcription factors.…”

EGFR, p53, IDH-1 and MDM2 immunohistochemical analysis in glioblastoma: therapeutic and prognostic correlation

“…Regarding the latter evaluation, we adapted the semi-quantitative classifications proposed by Giordana et al 14 and Korolopoulou et al 15 . Particularly, for each biological marker, the percentage of immunopositive cells was estimated by counting the number of immunopositive cells in ten high-power (40x) fields, which were systematically randomized throughout the section.…”

“…MDM2 also inhibits the function of other suppressor genes such as pRb, which in turn stimulates DNA synthesis in the S phase of mitosis 15 . Thus, changes in the levels of MDM2 may cause disturbance in cell cycle control and contribute to oncogenesis.…”

“…Thus, changes in the levels of MDM2 may cause disturbance in cell cycle control and contribute to oncogenesis. Usually MDM2 is associated with mutation of the p53 protein with direct and proportional relationship to the degree of malignancy and proliferation indices, specifically the number of mitoses per field 14,15 . Genetic alterations in MDM2 may be found in both primary and secondary forms of GBM.…”