Proliferative potential of sporadic and neurofibromatosis 2-associated schwannomas as studied by MIB-1 (Ki-67) and PCNA labeling.

Abstract

Neurofibromatosis 2 (NF2), a dominantly inherited disorder, is typically manifested as bilateral vestibular Schwannomas and predisposes to other nervous system tumors. Vestibular Schwannomas also occur sporadically but the onset is usually at an older age. Surgical and histological studies have shown that vestibular Schwannomas of NF2 patients are more invasive than sporadic Schwannomas and that the two groups also have morphological differences. We compared the proliferation activity of 26 vestibular Schwannomas (19 NF2 patients) to that of 27 sporadic cases using the Ki-67 (MIB-1) and PCNA (19A2) monoclonal antibodies. In addition, proliferation was assessed in 20 spinal benign Schwannomas, 4 spinal cellular Schwannomas and 3 spinal malignant peripheral nerve sheath tumors (MPNST). We found a significant difference in the proliferation potential between NF2 and sporadic vestibular Schwannomas (MIB-1-LI: 1.72 +/- 0.93 vs 0.95 +/- 0.57, p = 0.001; and PCNA-LI: 1.40 +/- 0.75 vs 0.81 +/- 0.52, p = 0.001). Age does not explain the detected difference in proliferation, since NF2 vestibular Schwannomas also had higher MIB-1 indices than 34 age-matched sporadic tumors. In spinal tumors, MPNST had higher MIB-1 indices than cellular Schwannomas, and therefore MIB-1 staining may be useful in distinguishing between them. Although the defective NF2 gene is important in the tumorigenesis of both NF2 and sporadic Schwannomas, our results suggest that there are differences in the molecular biology of these tumors.