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Effect of hypoxic microenvironment on expression of stem cell marker (nestin) in astrocytic tumors.

Research Abstract
Introduction: Gliomas account for 40% of the primary central nervous system tumors in western countries, and for about one-third (37.3%) in Egypt. Identification of the cellular origin of gliomas presents an opportunity for improving the treatment strategies. It has been postulated that astrocytomas may be originated from neural stem cells. Hypoxia-inducible factor-1[alpha] (HIF-1[alpha]) is considered one of the key hypoxia regulatory factors. Hypoxia may be a critical component of a stem cell niche and contributes to the tumor initiation and maintenance of cancer stem cells (CSCs). In the present study, we hypothesized that the expression of stem cell marker (nestin) and hypoxia marker (HIF-1[alpha]) may be upregulated with increasing grades of astrocytomas. In addition, there is a correlation between hypoxia and stem cell marker in all grades of astrocytomas in both tumor cells (TRCs) and vascular endothelial cells (VECs). To explore our hypothesis, this study was organized into specific aims: (a) analysis of the immunohistochemical expression of nestin and HIF-1[alpha] in different grades of astrocytomas and (b) analysis of the correlation between nestin and HIF-1[alpha] in different grades of astrocytomas. Materials and methods: Paraffin-embedded sections of 43 specimens of astrocytic tumors (nine pilocytic astrocytoma, 13 diffuse astrocytomas, seven anaplastic astrocytomas, and 14 glioblastoma multiforme) and six normal brain tissue (as a control) were stained with nestin and HIF-1[alpha] using standard immunohistochemical approaches. The immunoreactivity for nestin and HIF-1[alpha] in both TRCs and VECs was evaluated. Correlation between nestin and HIF-1[alpha] expression was also studied. Results: The expression of nestin in TRCs was present in 88.4% of patients. As compared with normal brain tissue, there was statistically significant (P0.01) gradual increase in the mean of nestin immunoreactivity score 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 HIF-1[alpha] was seen in 65.1% of studied patients. The immunoreactivity score of HIF-1[alpha] showed significant (P0.001) 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-1[alpha] in both TRCs and VECs (r=0.71 and 0.47, respectively, and P0.001 for both). Conclusion: Restricted oxygen conditions increase the CSC fraction. Determining the cross-talk between hypoxia and CSCs will enhance the understanding of tumorigenesis and may provide new therapeutic strategy. Intense expression of nestin in high-grade astrocytomas may be helpful in their diagnosis especially in small biopsy.
Research Authors
Elsers, Dalia A.; Elhakeem, Ahmed A.E.A.; Elgarory, Rabab M.H.; Kroosh, Sana S.
Research Department
Research Journal
Egyptian Journal of Pathology
Research Member
Research Pages
11-18
Research Rank
1
Research Vol
Volume 34 - Number 1
Research Website
http://ovidsp.tx.ovid.com/sp-3.15.1b/ovidweb.cgi
Research Year
2014

Evaluation of some histochemical and immunohistochemical criteria of round cell tumors of bone

Research Abstract
Background/aims The differential diagnosis of round cell tumors of bone (RCTB), Ewing sarcoma, small- cell osteosarcoma, mesenchymal chondrosarcoma, osteoblastoma, chondroblastoma, primary bone lymphoma, and multiple myeloma still remains a challenge. Given the significant differences in treatment, an accurate diagnosis is crucial. This study aimed to evaluate some histochemical and immunohistochemical criteria of RCTB. Participants and methods Periodic acid-Schiff (PAS), CD99, CD138, osteocalcin, and leukocyte common antigen (LCA) were evaluated in 113 patients with RCTB. Results PAS was positive in neoplastic cells of all Ewing sarcomas, 27% of osteosarcomas, 92% of chondrosarcomas, all osteoblastomas and chondroblastomas, and the osteoid tissue of all osteosarcomas and osteoblastomas. CD99 was positive in all Ewing sarcomas, in 11, 4, and 11% of osteoblastomas, multiple myelomas, and bone lymphomas, respectively. CD99 was higher in Ewing sarcoma than in other RCTB (P0.0001). Osteocalcin was positive in neoplastic cells of all osteosarcomas, osteoblastomas, and 20% of chondroblastomas, 84, and 78% of osteoid of osteosarcomas and osteoblastomas, respectively. CD138 was positive in all multiple myelomas, 12% of Ewing sarcomas, 20% of osteosarcomas, 44% of osteoblastomas, 8% of chondrosarcomas, and 40% of chondroblastomas. CD138 was higher in multiple myeloma (P0.0001) than in other RCTB. LCA positivity was higher (P0.01) in bone lymphomas (100%) than in multiple myelomas (73%). Conclusion PAS negativity excludes multiple myeloma and bone lymphoma from other RCTB that could be differentiated by LCA and CD138. CD99 positivity confirms the diagnosis of Ewing sarcoma. PAS could detect areas of osteoid in osteosarcoma and osteoblastoma. Osteocalcin suggests an osteogenic tumor origin: osteosarcoma/ osteoblastoma. Double negativity of CD99 and osteocalcin suggests a chondrogenic tumor origin: chondrosarcoma/chondroblastoma.
Research Authors
Eman M. S. Muhammad, Zeinab H. El-badawi, Sana S. Kroosh and Hassan H. Noaman
Research Department
Research Journal
Journal of the Arab Society for Medical Research
Research Pages
21-32
Research Rank
2
Research Vol
Volume 7
Research Website
http://www.journalonweb.com/jasmr/
Research Year
2012

Immunohistochemical Evaluation Of P53 Expression In Astrocytomas.

Research Abstract
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 astrocytomas 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&E stained sections from formalin fixed paraffin embedded blocks. P53 was immunohistochemically evaluated in selected 46 cases of astrocytomas and 12 cases reactive gliosis. Glioblastoma multiforme (WHO grade IV) was the predominant grade of astrocytomas. The mean age of patients with astrocytomas showed upergulation 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 upergulation with increasing grade. There was positive insignificant correlation between P53 expression and age, cellularity & mitosis and positive significant correlation between its expression and pleomorphism, microvascular proliferation & necrosis. All cases of gliosis except one showed negative P53 immunoreactivity. In conclusion: P53 protein alteration is an early event in tumorigenesis 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 gliosis from low grade astrocytomas.
Research Authors
Rabab M. H. El Ghorori,Yasser G. Abd El-Rhman, and Sana S. Kroosh
Research Department
Research Journal
Assiut Med. J.
Research Rank
2
Research Vol
Volume 29 - Number 2
Research Website
http://www.aun.edu.eg/faculty-medicine/journals.php
Research Year
2005

Immunohistochemical Evaluation Of P53 Expression In Astrocytomas.

Research Abstract
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 astrocytomas 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&E stained sections from formalin fixed paraffin embedded blocks. P53 was immunohistochemically evaluated in selected 46 cases of astrocytomas and 12 cases reactive gliosis. Glioblastoma multiforme (WHO grade IV) was the predominant grade of astrocytomas. The mean age of patients with astrocytomas showed upergulation 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 upergulation with increasing grade. There was positive insignificant correlation between P53 expression and age, cellularity & mitosis and positive significant correlation between its expression and pleomorphism, microvascular proliferation & necrosis. All cases of gliosis except one showed negative P53 immunoreactivity. In conclusion: P53 protein alteration is an early event in tumorigenesis 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 gliosis from low grade astrocytomas.
Research Authors
Rabab M. H. El Ghorori,Yasser G. Abd El-Rhman, and Sana S. Kroosh
Research Department
Research Journal
Assiut Med. J.
Research Member
Research Rank
2
Research Vol
Volume 29 - Number 2
Research Website
http://www.aun.edu.eg/faculty-medicine/journals.php
Research Year
2005

Immunohistochemical Evaluation Of P53 Expression In Astrocytomas.

Research Abstract
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 astrocytomas 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&E stained sections from formalin fixed paraffin embedded blocks. P53 was immunohistochemically evaluated in selected 46 cases of astrocytomas and 12 cases reactive gliosis. Glioblastoma multiforme (WHO grade IV) was the predominant grade of astrocytomas. The mean age of patients with astrocytomas showed upergulation 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 upergulation with increasing grade. There was positive insignificant correlation between P53 expression and age, cellularity & mitosis and positive significant correlation between its expression and pleomorphism, microvascular proliferation & necrosis. All cases of gliosis except one showed negative P53 immunoreactivity. In conclusion: P53 protein alteration is an early event in tumorigenesis 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 gliosis from low grade astrocytomas.
Research Authors
Rabab M. H. El Ghorori,Yasser G. Abd El-Rhman, and Sana S. Kroosh
Research Department
Research Journal
Assiut Med. J.
Research Rank
2
Research Vol
Volume 29 - Number 2
Research Website
http://www.aun.edu.eg/faculty-medicine/journals.php
Research Year
2005

Tuberculoma of the Orbit

Research Abstract
A 22-year-old male patient had proptosis and lower-lid mass extending to the orbit. Histopathology following surgical excision showed a characteristic picture of non-caseating granuloma. Acid-fast bacilli were seen in tissue sections. The patient responded to antituberculous therapy.
Research Authors
Massoud AM, Hassan SA, Kroosh SS
Research Department
Research Journal
Saudi Bull Ophthalmol
Research Pages
185-187
Research Rank
2
Research Vol
Volume 4 - Number 3
Research Year
1989

Tuberculoma of the Orbit

Research Abstract
A 22-year-old male patient had proptosis and lower-lid mass extending to the orbit. Histopathology following surgical excision showed a characteristic picture of non-caseating granuloma. Acid-fast bacilli were seen in tissue sections. The patient responded to antituberculous therapy.
Research Authors
Massoud AM, Hassan SA, Kroosh SS
Research Department
Research Journal
Saudi Bull Ophthalmol
Research Member
Research Pages
185-187
Research Rank
2
Research Vol
Volume 4 - Number 3
Research Year
1989

Tuberculoma of the Orbit

Research Abstract
A 22-year-old male patient had proptosis and lower-lid mass extending to the orbit. Histopathology following surgical excision showed a characteristic picture of non-caseating granuloma. Acid-fast bacilli were seen in tissue sections. The patient responded to antituberculous therapy.
Research Authors
Massoud AM, Hassan SA, Kroosh SS
Research Department
Research Journal
Saudi Bull Ophthalmol
Research Member
Ali Ahmed Masoud
Research Pages
185-187
Research Rank
2
Research Vol
Volume 4 - Number 3
Research Year
1989

Treatment of primary lymphoma of the lacrimal gland by surgical excision alone: A 5-year follow-up study

Research Abstract
PURPOSE . To evaluate the long-term efficacy of surgical excision alone in the treatment of non-Hodgkin¹s lymphoma localized to the lacrimal gland. MATERIALS AND METHODS . Thirteen patients with primary lacrimal gland lymphoma were included. The presumptive diagnosis was based on: (1) The painless and relatively slow onset of unilateral lacrimal gland swelling, mostly in elderly adults; (2) The CT pattern of a soft tissue mass in the lacrimal gland region with defined margins and molds to the globe; (3) The negative results of systemic work-up. The involved lacrimal gland was excised via an anterior trans-septal approach in 12 cases and by lateral canthotomy, upper cantholysis, and a trans-periosteal approach in one case. Following histopathologic confirmation of the diagnosis, no supplemental therapy was given. The patients were followed for a minimum of 5 years (5–8 years). RESULTS . In all patients, the excised lacrimal gland lymphoma was firm, nodular and appeared encapsulated. The histologic subtypes of the excised masses were: low-grade lymphomas in 11 cases (7 small lymphocytic, 3 plasmacytoid lymphocytic, 1 follicular small cleaved) and intermediate grade in 2 cases (1 follicular large cell and 1 diffuse small cleaved). No evidence of local recurrence or systemic dissemination was reported during the follow-up period in any of the patients. CONCLUSIONS . Surgical excision of the tumor is a new curative technique for lymphoma localized to the lacrimal gland without any other orbital or systemic involvement. By this technique, orbital radiotherapy and its potential ocular complications can be avoided. However, more study is recommended.
Research Authors
Abd El-Nasser A. Mohammad, Sana S. Kroosh
Research Department
Research Journal
Orbit
Research Pages
131-140
Research Rank
1
Research Vol
Volume 20 - Number 2
Research Website
http://informahealthcare.com/doi/abs/10.1076/orbi.20.2.131.2639
Research Year
2001

Treatment of primary lymphoma of the lacrimal gland by surgical excision alone: A 5-year follow-up study

Research Abstract
PURPOSE . To evaluate the long-term efficacy of surgical excision alone in the treatment of non-Hodgkin¹s lymphoma localized to the lacrimal gland. MATERIALS AND METHODS . Thirteen patients with primary lacrimal gland lymphoma were included. The presumptive diagnosis was based on: (1) The painless and relatively slow onset of unilateral lacrimal gland swelling, mostly in elderly adults; (2) The CT pattern of a soft tissue mass in the lacrimal gland region with defined margins and molds to the globe; (3) The negative results of systemic work-up. The involved lacrimal gland was excised via an anterior trans-septal approach in 12 cases and by lateral canthotomy, upper cantholysis, and a trans-periosteal approach in one case. Following histopathologic confirmation of the diagnosis, no supplemental therapy was given. The patients were followed for a minimum of 5 years (5–8 years). RESULTS . In all patients, the excised lacrimal gland lymphoma was firm, nodular and appeared encapsulated. The histologic subtypes of the excised masses were: low-grade lymphomas in 11 cases (7 small lymphocytic, 3 plasmacytoid lymphocytic, 1 follicular small cleaved) and intermediate grade in 2 cases (1 follicular large cell and 1 diffuse small cleaved). No evidence of local recurrence or systemic dissemination was reported during the follow-up period in any of the patients. CONCLUSIONS . Surgical excision of the tumor is a new curative technique for lymphoma localized to the lacrimal gland without any other orbital or systemic involvement. By this technique, orbital radiotherapy and its potential ocular complications can be avoided. However, more study is recommended.
Research Authors
Abd El-Nasser A. Mohammad, Sana S. Kroosh
Research Department
Research Journal
Orbit
Research Member
Research Pages
131-140
Research Rank
1
Research Vol
Volume 20 - Number 2
Research Website
http://informahealthcare.com/doi/abs/10.1076/orbi.20.2.131.2639
Research Year
2001
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