Mesenchymal-Type Genetic Mutations Are Likely Prerequisite for Glioblastoma Multiforme to Metastasize Outside the Central Nervous System: An Original Case Series and Systematic Review of the Literature
Bryce J. Laurin , Randall Treffy , Jennifer M. Connelly , Michael Straza , Wade M. Mueller , Max O. Krucoff
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引用次数: 0
Abstract
Background
Glioblastoma multiforme (GBM) is the most aggressive and prevalent type of malignant brain tumor, yet it metastasizes outside the central nervous system (CNS) in only 0.4% of cases. Little is known about what enables this subset of GBMs to take root outside the CNS, but genetic mutations likely play a role.
Methods
We conducted a PRISMA-compliant systematic review of metastatic GBM wherein we reviewed 3579 search results and 1080 abstracts, analyzing data from 139 studies and 211 unique patients. In addition, we describe 4 cases of patients with pathologically confirmed GBM metastases outside the CNS treated at our institution.
Results
We found that metastases were discovered near previous surgical sites in at least 36.9% of cases. Other sites of metastasis included bone (47.9%), lung (25.6%), lymph nodes (25.1%), scalp (19.2%), and liver (14.2%). On average, metastases were diagnosed 12.1 months after the most recent resection, and the mean survival from discovery was 5.7 months. In our patients, primary GBM lesions showed mutations in NF1, TERT, TP53, CDK4, and RB1/PTEN genes. Unique to the metastatic lesions were amplifications in genes such as p53 and PDGFRA/KIT, as well as increased vimentin and Ki-67 expression.
Conclusions
There is strong evidence that GBMs acquire novel mutations to survive outside the CNS. In some cases, tumor cells likely mutate after seeding scalp tissue during surgery, and in others, they mutate and spread without surgery. Future studies and genetic profiling of primary and metastatic lesions may help uncover the mechanisms of spread.
期刊介绍:
World Neurosurgery has an open access mirror journal World Neurosurgery: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review.
The journal''s mission is to:
-To provide a first-class international forum and a 2-way conduit for dialogue that is relevant to neurosurgeons and providers who care for neurosurgery patients. The categories of the exchanged information include clinical and basic science, as well as global information that provide social, political, educational, economic, cultural or societal insights and knowledge that are of significance and relevance to worldwide neurosurgery patient care.
-To act as a primary intellectual catalyst for the stimulation of creativity, the creation of new knowledge, and the enhancement of quality neurosurgical care worldwide.
-To provide a forum for communication that enriches the lives of all neurosurgeons and their colleagues; and, in so doing, enriches the lives of their patients.
Topics to be addressed in World Neurosurgery include: EDUCATION, ECONOMICS, RESEARCH, POLITICS, HISTORY, CULTURE, CLINICAL SCIENCE, LABORATORY SCIENCE, TECHNOLOGY, OPERATIVE TECHNIQUES, CLINICAL IMAGES, VIDEOS