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September 06-07, 2018 | Edinburgh, Scotland
Pathology and Surgical Pathology
International Conference on
Journal of Pathology and Disease Biology | Volume 2
Ahmed A S Elhakeem
Dalia A Elsers, Rabab M H and Elgaroryand Sana S Kroosh
Al-Azhar University, Egypt
Effect of hypoxic microenvironment on expression of stem cell marker (nestin) in
astrocytic tumors
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-1a (HIF-1a) 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-1a) 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-1a in different grades of astrocytomas and (b)
analysis of the correlation between nestin and HIF-1a 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-1a using standard
immunohistochemical approaches. The immunoreactivity
for nestin and HIF-1a in both TRCs and VECs was evaluated.
Correlation between nestin and HIF-1a 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 (P < 0.01) 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-1a was seen in 65.1% of studied patients.
The immunoreactivity score of HIF-1a 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-1a
in both TRCs and VECs (r =0.71 and 0.47, respectively, and P
< 0.001 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.
Speaker Biography
Ahmed A S Elhakeem is working as a lecturer at the Department of Pathology
of Assiut University in Egypt. His professional affiliation entails being a member
of the International Society of Neuropathology, Egyptian society of Pathology
and Egyptian society of progenitor cell research. He excels in the subspecialty
of Neuropathology with over 10 years of experience in the diagnosis of
brain and spinal lesions. His research interest also covers cancer stem cells.
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