Correlation of expression pattern of aquaporin-1 in primary central nervous system tumors with tumor type, grade, proliferation, microvessel density, contrast-enhancement and perilesional edema.
OBJECTIVE
Brain edema, a hallmark of malignant brain tumors, continues to be a major cause of mortality. The underlying molecular mechanisms are poorly understood and thought to be mediated through membrane water-channels: aquaporins (AQP1,4,9). The abnormal upregulation of AQP1 in certain glial neoplasms has suggested a potential role in tumor pathogenesis, apart from being a novel target for newer therapeutic regimen. This study was undertaken to evaluate the expression of AQP1 in primary CNS tumors of various histologic types and grades, and its correlation with contrast-enhancement, perilesional edema, histomorphology, proliferation index and microvessel density.


METHODS
Biopsy tissues from 30 patients (10 each from gliomas, meningiomas and other primary CNS tumors) were studied. Autopsy brain sections served as control. AQP1-immunoreactivity was correlated with histomorphology, radiology, proliferation index and microvessel density (MVD).


RESULTS
AQP1 expression was increased in gliomas and ependymal tumors as compared to meningiomas. Intratumoral expression was homogenous in high-grade and membranous in low-grade neoplasms, while peritumoral areas showed expression around vessels and reactive astrocytes. High-grade tumors showed peritumoral upregulation, while low-grade had intense intratumoral expression. A trend of positive correlation was observed between AQP1-immunopositivity and increasing grade, higher MIB-1LI, increasing contrast-enhancement and more perilesional edema, and elevated MVD with raised AQP1:MVD ratio.


CONCLUSIONS
AQP1-immunoexpression had a good correlation with high-grade tumors. AQP-upregulation in perilesional areas of high-grade tumors suggests its role in vasogenic edema. Further studies involving other AQP molecules, vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 α (HIF-1α) should be undertaken to evaluate its possible role as a potential surrogate marker of high-grade tumors heralding poor outcome, inhibition of which may serve as the basis for future targeted therapy.
Department of Pathology, Armed Forces Medical College, Pune, India. debprabal@gmail.com
Prabal
P
Deb
Seerat
S
Pal
Vibha
V
Dutta
Dibyajyoti
D
Boruah
Vijai M
VM
Chandran
Harjinder S
HS
Bhatoe
D000293:Adolescent; D000328:Adult; D000368:Aged; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism*; D016543:Central Nervous System Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D004487:Edema; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D055806:Microvessels; D008875:Middle Aged; D060787:Neoplasm Grading; D055815:Young Adult
D051398:Aquaporin 1