gms | German Medical Science

Objective: NCAM is one major interaction molecule within the brain and it is expressed in neurons and glia. For the first time this study evaluates the relevance of NCAM in glioma prognosis estimation and for the investigation of the glioblastoma invasion zone – a tumor area that could not be analyzed until now.

Methods: We included 95 gliomas, 6 brain metastases, 7 meningiomas, 4 pituitary adenomas, and 18 controls. 35 glioblastoma specimens contained tumor tissue and peritumoral brain parenchyma. In addition, 4 nude rats with human glioblatomas were included. All tumors were stained with primary antibodies against NCAM, MMP2, CD31, Ki67, factor X and PAR1.

Results: Human glioblastomas expressed significantly less NCAM than did astrocytomas grade III and grade II. Normal brain tissue expressed most NCAM. With respect to other brain tumors, metastases had the lowest NCAM expression and differed significantly from meningiomas, gliomas and pituitary adenomas. Especially in glioblastomas, we were able to identify the tumor border zone by NCAM reactivity. That was possible even macroscopically, which strengthens the usefulness of NCAM reaction during brain tumor surgery. We could identify three major invasion patterns in human glioblastomas with all their transitions. The diffuse glioblastoma cell invasion made up the majority of cases, followed by diffusely infiltrating tumor cell nests. The minority of glioblastomas did not show a clear tumor invasion and demonstrated a relatively sharp border zone instead of this. All results could be confirmed in the nude rat mode. This makes the definite tumor border identification by anti-human and anti-rat antibodies possible. With respect to the expression of MMP2, factor X, and PAR1, we found an increased tumor cell expression within the tumor mass and the invasion area. In addition, MMP2 was significantly increased within endothelial cells of the tumor mass and its invasion area in comparison to their negativity in the peritumoral area.

Conclusions: NCAM enables the differentiation of malignant and benign gliomas as a new prognostic tool. It visualizes the border zone of glioblastomas and distinct invasion paradigms. This makes the investigation of the tumor invasion zone and its differentiation from the tumor mass and the peritumoral zone possible. By use of NCAM as a visualization tool, we found specific profiles for MMP2, the coagulation factor X, and its receptor PAR1 within glioblastomas and their neighbourhood.