Association between laminin-8 and glial tumor grade, recurrence, and patient survival.
BACKGROUND
The authors previously sought to identify novel markers of glioma invasion and recurrence. Their research demonstrated that brain gliomas overexpressed a subset of vascular basement components, laminins, that contained the alpha4 chain. One of these laminins, laminin-8, was found to be present in highly invasive and malignant glioblastoma multiforme (GBM) (Grade 4 astrocytoma); its expression was associated with a decreased time to tumor recurrence, and it was found in vitro to promote invasion of GBM cell lines.


METHODS
In the current study, the authors studied glial tumors of different grades in an attempt to correlate laminin-8 expression with tumor recurrence and patient survival. Immunohistochemistry and Western blot analysis were used to detect laminin isoforms of interest.


RESULTS
Using immunohistochemistry and Western blot analysis, the authors confirmed high levels of laminin-8 expression in approximately 75% of the GBM cases examined and in their adjacent tissues, whereas astrocytomas of lower grades expressed for the most part a different isoform, laminin-9, which also was found in low amounts in normal brain tissue and benign meningiomas. Overexpression of laminin-8 in GBM was found to be associated with a statistically significant shorter time to tumor recurrence (P < 0.0002) and a decreased patient survival time (P < 0.015).


CONCLUSIONS
The data suggest that laminin-8, which may facilitate tumor invasion, contributes to tumor regrowth after therapy. Laminin-8 may be used as a predictor of tumor recurrence and patient survival and as a potential molecular target for glioma therapy.
Ljubimova
Julia Y
JY
Department of Surgery, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. ljubimovaj@cshs.org
Fugita
Manabu
M
Khazenzon
Natalya M
NM
Das
Asha
A
Pikul
Brian B
BB
Newman
Daniel
D
Sekiguchi
Kiyotoshi
K
Sorokin
Lydia M
LM
Sasaki
Takako
T
Black
Keith L
KL
D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology; D005910:Glioma / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D007797:Laminin; C110308:laminin 8