Pińa Batista K M, Vega I F, de Eulate-Beramendi S A, Morales Jcg, Kurbanov A, Asnel D, Meilan A, Astudillo A
Kelvin Manuel Piña Batista, MD, PhD, Department of Neurosurgery, Hospital Universitario Central de Asturias, e-mail:
Folia Neuropathol. 2015;53(1):52-9. doi: 10.5114/fn.2015.49974.
Glioblastoma multiforme (GBM), a highly aggressive brain cancer characterized by uncontrolled proliferation, resistance to cell death, angiogenesis, and vascular edema, remains one of the deadliest types of cancer. The subventricular zone (SVZ) harbors cells with great proliferative potential, and the microenvironment within the SVZ is permissive to growth and proliferation. This neurogenic niche is suspected to be a vulnerable site for the origin of subtypes of GBM. The aim of our study was to determine the immunohistochemical expression of mIDH1 and YKL40 in relationship to the SVZ of GBMs. YKL40, also known as chitinase-like protein 1, is included as a mesenchymal marker and associated with a poor prognosis. The protein is a secreted inflammatory molecule with no chitinolytic activity. However, the mutation of IDH1 (mIDH1) has been found in the cytoplasm and peroxisomes of 70-80% of secondary GBMs. In our study we found that YKL40-positive GBM is significantly linked to SVZ types IV and V (p < 0.0001). Our results show the diversity among GBMs related to the SVZ, which should be considered in the design of future targeted therapies. There was a significant impact of patient age, mIDH1 positivity, SVZ type III, and chemoradiotherapy on overall survival.
多形性胶质母细胞瘤（GBM）是一种极具侵袭性的脑癌，其特征为细胞增殖失控、对细胞死亡具有抗性、血管生成以及血管性水肿，它仍然是最致命的癌症类型之一。脑室下区（SVZ）含有具有强大增殖潜力的细胞，并且SVZ内的微环境有利于生长和增殖。这个神经源性生态位被怀疑是GBM亚型起源的一个脆弱部位。我们研究的目的是确定mIDH1和YKL40与GBM的SVZ相关的免疫组化表达。YKL40，也被称为几丁质酶样蛋白1，被列为一种间充质标志物且与预后不良相关。该蛋白是一种无几丁质分解活性的分泌性炎症分子。然而，在70 - 80%的继发性GBM的细胞质和过氧化物酶体中发现了IDH1（mIDH1）的突变。在我们的研究中，我们发现YKL40阳性的GBM与IV型和V型SVZ显著相关（p < 0.0001）。我们的结果显示了与SVZ相关的GBM之间的多样性，这在未来靶向治疗的设计中应予以考虑。患者年龄、mIDH1阳性、SVZ III型以及放化疗对总生存期有显著影响。
