Over-expression of laminin-8 by malignant gliomas predicts tumor grade, risk for recurrence, and patient survival, according to an article in the August issue of Cancer. The conversion from low-level expression of laminin-9 in normal and low-grade tumors to increasing over-expression of laminin-8 suggests that a molecular change in the basement membrane may contribute to tumor cell infiltration into nearby healthy tissue.

The average survival time for patients with Grade 1 or Grade 2 gliomas is 6 to 8 years. For Grade 3 gliomas, survival time decreases to 3 years, and Grade 4 tumors (or glioblastoma multiforme), are associated with a survival length that ranges from 12 to 18 months.

In the current study, American researchers, in conjunction with colleagues in Japan, Sweden, and Germany, analyzed a variety of gliomas of both high and low grades, as well as normal brain tissue samples. Low-grade astrocytomas and normal brain tissue were found to express very low levels of laminin-9 and virtually no laminin-8. The levels of expression of both variants increased in Grade 3 gliomas, and as gliomas progressed to Grade 4, laminin-8 expression increased significantly and laminin-9 levels declined.

The particular isoform (laminin-8 or laminin-9) predominantly expressed in Grade 4 gliomas (glioblastoma multiforme) appeared to correlate with time to recurrence after tumor-removal surgery. Among patients with high laminin-8 expression, tumors recurred about 4 months after surgery, compared with more than 11 months among patients whose tumors expressed laminin-9 predominantly. Patients with higher levels of laminin-8 also had shorter lengths of survival, averaging about 11 months, compared with 16.7 months when laminin-9 was predominant.

“Historically, the diagnosis of glioblastoma multiforme has come with an extremely poor prognosis, and traditional treatments have had very limited impact on patient survival,” said Keith L. Black, MD.

“Only in recent years have we begun to see progress, which is coming from a better understanding of genetic, molecular and immunologic changes that enable these deadly tumors to grow. Although a number of genes and proteins have been identified as having altered expression in glial tumors, few have become reliable indicators that can be used to improve diagnosis, prognosis and treatment,” added Black.

Julia Y. Ljubimova, MD, PhD, lead author of the article, said over-expression of laminin-8 may prove to be one of those important markers. Taken in consideration with other genes known to support tumor growth, it may give clinicians measurable clues for predicting recurrence and survival times of patients with high-grade gliomas.

“The switch from laminin-9 to laminin-8 expression, with its gradual increase from a low level of expression in low-grade tumors to a moderate level of expression in Grade 3 gliomas to a significantly high level of expression in 74 percent of glioblastoma multiforme, may be associated with the development of new tumor-feeding blood vessels, contributing to tumor aggressiveness,” Ljubimova said. “Therefore, laminin-8 appears to be a promising marker of tumor progression.

Perhaps more importantly, we hypothesize that if laminin-8 plays a major role in tumor progression and recurrence, it could be an important target for the development of new therapies.”