surgical biopsy from astrocytomas is usually obtained from enhanced lesion but sometimes may include fragments of apparently normal brain tissue/peritumoral areas. We hypothesize that the evaluation of these fragments for presence of cancer stem cells may have prognostic and /or diagnostic implication. This work has been planned to 1) verify nestin and hypoxia inducible factor-1α location in apparently normal brain tissue/peritumoral areas and its relation to the presence of neoplastic cells in these fragments and 2) analyze the correlation between nestin and hypoxia inducible factor-1 α expression in apparently normal brain tissue/peritumoral areas adjacent to different grades of astrocytomas. Material and Methods: Paraffin-embedded sections of selected thirty specimens of astrocytomas contain apparently normal brain tissue/peritumoral areas (12 diffuse astrocytomas, 6 anaplastic astrocytomas and 12 glioblastoma multiforme) were stained with nestin and hypoxia inducible factor-1α using standard immunohistochemical approaches. The immunoreactivity for nestin and Hypoxia-inducible factor -1 α was evaluated. Results: Compared to nearby astrocytomas, nestin immunoreactivity was scarcely expressed in apparently normal brain tissue/peritumoral tissue. There was statistically significant (P =0.03) gradual increase of mean percentage of nestin positive cells that present in these fragments with increasing grade of the adjacent astrocytomas from diffuse astrocytoma to anaplastic astrocytoma to glioblastoma multiforme (27.1± 4, 38.3±3 and 47.5±5.9, respectively). There was statistically insignificant (P 0.1) gradual increase of mean percentage of hypoxia inducible factor-1α positive neoplastic cells that infiltrate peritumoral areas with increasing grade of the adjacent astrocytomas. There was statistically significant gradual increase of counting of microvessels that showed positivity for nestin and hypoxia inducible factor-1α expression with increasing grade of the adjacent astrocytomas (P=0.008, P=0.01, respectively). Conclusion: Nestin and hypoxia inducible factor-1α was expressed in apparently normal brain tissue/peritumoral tissue adjacent to astrocytomas. Positivity for nestin in apparently normal fragments may indicate premalignant changes or nearby tumor when a biopsy contain only apparently normal brain tissue. Evaluation of nestin expression in peritumoral areas may have prognostic value as it may be an indicator for rapid recurrence and resistance of treatment.

surgical biopsy from astrocytomas is usually obtained from enhanced lesion but sometimes may include fragments of apparently normal brain tissue/peritumoral areas. We hypothesize that the evaluation of these fragments for presence of cancer stem cells may have prognostic and /or diagnostic implication. This work has been planned to 1) verify nestin and hypoxia inducible factor-1α location in apparently normal brain tissue/peritumoral areas and its relation to the presence of neoplastic cells in these fragments and 2) analyze the correlation between nestin and hypoxia inducible factor-1 α expression in apparently normal brain tissue/peritumoral areas adjacent to different grades of astrocytomas. Material and Methods: Paraffin-embedded sections of selected thirty specimens of astrocytomas contain apparently normal brain tissue/peritumoral areas (12 diffuse astrocytomas, 6 anaplastic astrocytomas and 12 glioblastoma multiforme) were stained with nestin and hypoxia inducible factor-1α using standard immunohistochemical approaches. The immunoreactivity for nestin and Hypoxia-inducible factor -1 α was evaluated. Results: Compared to nearby astrocytomas, nestin immunoreactivity was scarcely expressed in apparently normal brain tissue/peritumoral tissue. There was statistically significant (P =0.03) gradual increase of mean percentage of nestin positive cells that present in these fragments with increasing grade of the adjacent astrocytomas from diffuse astrocytoma to anaplastic astrocytoma to glioblastoma multiforme (27.1± 4, 38.3±3 and 47.5±5.9, respectively). There was statistically insignificant (P 0.1) gradual increase of mean percentage of hypoxia inducible factor-1α positive neoplastic cells that infiltrate peritumoral areas with increasing grade of the adjacent astrocytomas. There was statistically significant gradual increase of counting of microvessels that showed positivity for nestin and hypoxia inducible factor-1α expression with increasing grade of the adjacent astrocytomas (P=0.008, P=0.01, respectively). Conclusion: Nestin and hypoxia inducible factor-1α was expressed in apparently normal brain tissue/peritumoral tissue adjacent to astrocytomas. Positivity for nestin in apparently normal fragments may indicate premalignant changes or nearby tumor when a biopsy contain only apparently normal brain tissue. Evaluation of nestin expression in peritumoral areas may have prognostic value as it may be an indicator for rapid recurrence and resistance of treatment.

surgical biopsy from astrocytomas is usually obtained from enhanced lesion but sometimes may include fragments of apparently normal brain tissue/peritumoral areas. We hypothesize that the evaluation of these fragments for presence of cancer stem cells may have prognostic and /or diagnostic implication. This work has been planned to 1) verify nestin and hypoxia inducible factor-1α location in apparently normal brain tissue/peritumoral areas and its relation to the presence of neoplastic cells in these fragments and 2) analyze the correlation between nestin and hypoxia inducible factor-1 α expression in apparently normal brain tissue/peritumoral areas adjacent to different grades of astrocytomas. Material and Methods: Paraffin-embedded sections of selected thirty specimens of astrocytomas contain apparently normal brain tissue/peritumoral areas (12 diffuse astrocytomas, 6 anaplastic astrocytomas and 12 glioblastoma multiforme) were stained with nestin and hypoxia inducible factor-1α using standard immunohistochemical approaches. The immunoreactivity for nestin and Hypoxia-inducible factor -1 α was evaluated. Results: Compared to nearby astrocytomas, nestin immunoreactivity was scarcely expressed in apparently normal brain tissue/peritumoral tissue. There was statistically significant (P =0.03) gradual increase of mean percentage of nestin positive cells that present in these fragments with increasing grade of the adjacent astrocytomas from diffuse astrocytoma to anaplastic astrocytoma to glioblastoma multiforme (27.1± 4, 38.3±3 and 47.5±5.9, respectively). There was statistically insignificant (P 0.1) gradual increase of mean percentage of hypoxia inducible factor-1α positive neoplastic cells that infiltrate peritumoral areas with increasing grade of the adjacent astrocytomas. There was statistically significant gradual increase of counting of microvessels that showed positivity for nestin and hypoxia inducible factor-1α expression with increasing grade of the adjacent astrocytomas (P=0.008, P=0.01, respectively). Conclusion: Nestin and hypoxia inducible factor-1α was expressed in apparently normal brain tissue/peritumoral tissue adjacent to astrocytomas. Positivity for nestin in apparently normal fragments may indicate premalignant changes or nearby tumor when a biopsy contain only apparently normal brain tissue. Evaluation of nestin expression in peritumoral areas may have prognostic value as it may be an indicator for rapid recurrence and resistance of treatment.

Gliomas account for 40% of primary central nervous system tumors in western countries, and about one third (37.3%) in Egypt. Identification of the cellular origin of gliomas, presents an opportunity for improving treatment strategies. It has been postulated that astrocytomas (represent 75% of gliomas) may be originated from cancer stem cells. Hypoxia may be a critical component of a stem cell niche and contributes to the tumor initiation and maintenance of cancer stem cells. In the present study, we hypothesized that the expression of stem cell marker (nestin) and hypoxia marker (Hypoxia-inducible factor-1α, HIF-1α) may be upregulated in astrocytomas. To explore our hypothesis, this work has been conducted to analyze the immunohistochemical profile of nestin and HIF- 1α in astrocytomas and to correlate their expression in different grades of the tumor. Material and methods: Paraffin-embedded sections of forty three specimens of astrocytic tumors (9 pilocytic astrocytoma, 13 diffuse astrocytomas, 7 anaplastic astrocytomas, and 14 glioblastoma multiforme) and 6 normal brain tissue (as a control) were stained with nestin and HIF-1α using standard immunohistochemical approaches. The immunoreactivity for nestin and HIF -1 α in both tumor cells and vascular endothelial cells were evaluated. Correlation between nestin and HIF-1 α expression was also studied. Results: The expression of nestin in tumor cells was present in 88.4% of cases. As compared to normal brain tissue, there was statistically significant (P 0.01) gradual increase in the mean of nestin immunoreactivity score (IRS) with increasing grade of the studied astrocytomas (I –IV) (0.0+0.0, 1.7+1.8, 2.5+1.6, 5.7+3.2, and 7.8+2.5, respectively). The expression of hypoxia-inducible factor -1 α was seen in 65.1% of studied cases. The IRS of HIF -1 α showed significant (p >0.001) difference between low grade astrocytomas (pilocytic astrocytoma and diffuse astrocytomas) and high grade astrocytomas (anaplastic astrocytomas and glioblastoma multiforme). There was statistically significant positive correlation between expression of nestin and HIF-1α in both tumor cells and vascular endothelial cells (r =0.71, r=0.47 respectively and P 0.001 for both). In conclusion: Intense expression of nestin in high grade astrocytomas may be helpful in their diagnosis especially in small biopsy. Determining the crosstalk between hypoxia and cancer stem cells will enhance the understanding of tumorigenesis and may provide new therapeutic strategy.

Gliomas account for 40% of primary central nervous system tumors in western countries, and about one third (37.3%) in Egypt. Identification of the cellular origin of gliomas, presents an opportunity for improving treatment strategies. It has been postulated that astrocytomas (represent 75% of gliomas) may be originated from cancer stem cells. Hypoxia may be a critical component of a stem cell niche and contributes to the tumor initiation and maintenance of cancer stem cells. In the present study, we hypothesized that the expression of stem cell marker (nestin) and hypoxia marker (Hypoxia-inducible factor-1α, HIF-1α) may be upregulated in astrocytomas. To explore our hypothesis, this work has been conducted to analyze the immunohistochemical profile of nestin and HIF- 1α in astrocytomas and to correlate their expression in different grades of the tumor. Material and methods: Paraffin-embedded sections of forty three specimens of astrocytic tumors (9 pilocytic astrocytoma, 13 diffuse astrocytomas, 7 anaplastic astrocytomas, and 14 glioblastoma multiforme) and 6 normal brain tissue (as a control) were stained with nestin and HIF-1α using standard immunohistochemical approaches. The immunoreactivity for nestin and HIF -1 α in both tumor cells and vascular endothelial cells were evaluated. Correlation between nestin and HIF-1 α expression was also studied. Results: The expression of nestin in tumor cells was present in 88.4% of cases. As compared to normal brain tissue, there was statistically significant (P 0.01) gradual increase in the mean of nestin immunoreactivity score (IRS) with increasing grade of the studied astrocytomas (I –IV) (0.0+0.0, 1.7+1.8, 2.5+1.6, 5.7+3.2, and 7.8+2.5, respectively). The expression of hypoxia-inducible factor -1 α was seen in 65.1% of studied cases. The IRS of HIF -1 α showed significant (p >0.001) difference between low grade astrocytomas (pilocytic astrocytoma and diffuse astrocytomas) and high grade astrocytomas (anaplastic astrocytomas and glioblastoma multiforme). There was statistically significant positive correlation between expression of nestin and HIF-1α in both tumor cells and vascular endothelial cells (r =0.71, r=0.47 respectively and P 0.001 for both). In conclusion: Intense expression of nestin in high grade astrocytomas may be helpful in their diagnosis especially in small biopsy. Determining the crosstalk between hypoxia and cancer stem cells will enhance the understanding of tumorigenesis and may provide new therapeutic strategy.

Gliomas account for 40% of primary central nervous system tumors in western countries, and about one third (37.3%) in Egypt. Identification of the cellular origin of gliomas, presents an opportunity for improving treatment strategies. It has been postulated that astrocytomas (represent 75% of gliomas) may be originated from cancer stem cells. Hypoxia may be a critical component of a stem cell niche and contributes to the tumor initiation and maintenance of cancer stem cells. In the present study, we hypothesized that the expression of stem cell marker (nestin) and hypoxia marker (Hypoxia-inducible factor-1α, HIF-1α) may be upregulated in astrocytomas. To explore our hypothesis, this work has been conducted to analyze the immunohistochemical profile of nestin and HIF- 1α in astrocytomas and to correlate their expression in different grades of the tumor. Material and methods: Paraffin-embedded sections of forty three specimens of astrocytic tumors (9 pilocytic astrocytoma, 13 diffuse astrocytomas, 7 anaplastic astrocytomas, and 14 glioblastoma multiforme) and 6 normal brain tissue (as a control) were stained with nestin and HIF-1α using standard immunohistochemical approaches. The immunoreactivity for nestin and HIF -1 α in both tumor cells and vascular endothelial cells were evaluated. Correlation between nestin and HIF-1 α expression was also studied. Results: The expression of nestin in tumor cells was present in 88.4% of cases. As compared to normal brain tissue, there was statistically significant (P 0.01) gradual increase in the mean of nestin immunoreactivity score (IRS) with increasing grade of the studied astrocytomas (I –IV) (0.0+0.0, 1.7+1.8, 2.5+1.6, 5.7+3.2, and 7.8+2.5, respectively). The expression of hypoxia-inducible factor -1 α was seen in 65.1% of studied cases. The IRS of HIF -1 α showed significant (p >0.001) difference between low grade astrocytomas (pilocytic astrocytoma and diffuse astrocytomas) and high grade astrocytomas (anaplastic astrocytomas and glioblastoma multiforme). There was statistically significant positive correlation between expression of nestin and HIF-1α in both tumor cells and vascular endothelial cells (r =0.71, r=0.47 respectively and P 0.001 for both). In conclusion: Intense expression of nestin in high grade astrocytomas may be helpful in their diagnosis especially in small biopsy. Determining the crosstalk between hypoxia and cancer stem cells will enhance the understanding of tumorigenesis and may provide new therapeutic strategy.

Purpose: To analyze the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) and mean vascular count (MVC) in both serous and mucinous ovarian tumors. The correlation of these markers with clinicopatological characteristics was also evaluated. Methods: Ninety five paraffin-embedded sections of ovarian tumors were stained for MMP-2, MMP-9, VEGF and CD34 using standard immunohistochemistry. The intensity and percentage of positive cells were evaluated using H-score for MMPs and VEGF. The MVC as stained by CD34 (X 400) was also evaluated. Correlations between H-scores of MMP-2, MMP-9 with VEGF H-score were evaluated. The relationships between the above markers with clinicopathological characteristics and the correlations between VEGF with MVC were also studied. Results: There is a significant increase in H-scores of tumor and stromal cells with the transitions through tumorigenesis phases (P0.0001 for all markers). Serous tumors showed significantly higher expression of VEGF, MMP-2 and MMP-9 and MVC as compared with mucinous tumors. The expression of all markers was significantly correlated with development of ascites, peritoneal deposits , grading and staging of tumors. Conclusion: MMP-2, MMP-9 and VEGF are expressed by both tumor and stromal cells of ovarian tumors and their expressions are associated with the transitions from benign, through borderline, to malignant nature. The above markers are correlated with clinicopathological characteristics.

Purpose: To analyze the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) and mean vascular count (MVC) in both serous and mucinous ovarian tumors. The correlation of these markers with clinicopatological characteristics was also evaluated. Methods: Ninety five paraffin-embedded sections of ovarian tumors were stained for MMP-2, MMP-9, VEGF and CD34 using standard immunohistochemistry. The intensity and percentage of positive cells were evaluated using H-score for MMPs and VEGF. The MVC as stained by CD34 (X 400) was also evaluated. Correlations between H-scores of MMP-2, MMP-9 with VEGF H-score were evaluated. The relationships between the above markers with clinicopathological characteristics and the correlations between VEGF with MVC were also studied. Results: There is a significant increase in H-scores of tumor and stromal cells with the transitions through tumorigenesis phases (P0.0001 for all markers). Serous tumors showed significantly higher expression of VEGF, MMP-2 and MMP-9 and MVC as compared with mucinous tumors. The expression of all markers was significantly correlated with development of ascites, peritoneal deposits , grading and staging of tumors. Conclusion: MMP-2, MMP-9 and VEGF are expressed by both tumor and stromal cells of ovarian tumors and their expressions are associated with the transitions from benign, through borderline, to malignant nature. The above markers are correlated with clinicopathological characteristics.