The biology of meningiomas

Abstract

Biochemical and molecular biological analyses of central nervous system tumors have progressed considerably in the last two decades. It may soon be possible to reclassify tumors according to biochemical or genetic criteria that relate directly to the tumor's individual biologic potential. Beyond informing a prognosis, these studies may also indicate strategies by which a tumor's biologic destiny can be altered or interrupted. With regard to meningiomas, this promise has not yet been fulfilled, although new agents such as mifepristone are achieving modest success. The greatest efforts thus far have been devoted to the study of sex steroid receptors. Historically, interest in this line of inquiry was enlivened by perceived parallels with hormone receptors identified in breast cancer tissue. Although investigative results have varied widely, a consensus has emerged that a majority of meningiomas harbor genuine PR and AR. These results are now confirmed by powerful molecular biologic techniques that interrogate for the presence of specific receptor mRNA. Whether these proteins represent functioning receptors remains highly controversial. Neither in vitro stimulation studies nor clinical experience has disclosed a consistent or convincing pattern of response to resolve this question. The possibility exists that the expression of these specific receptor proteins is but an epiphenomenon, the signature of the underlying neoplastic process, but functionally disconnected from its initiation or maintenance. The role that polypeptide growth factors and neurohumoral agents have in the biology of meningiomas is not yet clear but is an area of intense investigative effort. Attempts to elucidate the activity and interplay of these substances in in vitro cell culture assays have yielded inconsistent outcomes. These assays are extremely complex, and the results can be dramatically influenced by a host of recognized and unrecognized variables making interlaboratory comparisons difficult. A fundamental unknown is the fidelity of such cell culture assays in mirroring the in vivo biology of a given tumor. At least some of these difficulties are overcome in the direct molecular analysis of the tumor genome, which identifies specific genes and gene products in the primary specimen.(ABSTRACT TRUNCATED AT 400 WORDS)