Department of Pulmonology, Kenézy Gyula Hospital, Debrecen, Hungary.
Pathol Oncol Res. 2012 Apr;18(2):413-20. doi: 10.1007/s12253-011-9461-0. Epub 2011 Oct 14.
The extent of tumor removal determines the effectiveness of postoperative oncotherapy. This is especially true for primary brain tumors, where peritumoral invasion usually makes radical resection impossible. The aim of the study was to determinate the specific expression pattern of invasion related molecules of different intracranial tumors and to identify molecules that are principally responsible for the peritumoral invasiveness of grade II astrocytoma mRNA expression of 26 extracellular matrix (ECM) molecules was determined in tissue samples from grade II astrocytoma, schwannoma, intracerebral metastases of non-small cell lung cancer and normal brain. Immunohistochemical staining for brevican, neurocan, tenascin-C and versican was also performed for each tumor group. Comparing astrocytoma to metastasis, schwannoma and normal brain; and metastasis and schwannoma to normal brain, 22, 17, 20, 21, and 19 molecules, respectively, were found to be significantly overexpressed at the mRNA level. Cluster analysis of mRNA expression showed a specific gene expression pattern for each histological group. Four molecules of 26 were found to be associated to astrocytoma. Immunohistochemical staining confirmed the results of the mRNA analysis at the protein level. Tumors of different origin have a specific invasive phenotype that can evidently determinate on gene expression level. This characteristic expression pattern of the invasion-related molecules might help to screen exact targets for anti-invasion drugs. In case of low-grade astrocytoma. brevican, neurocan, tenascin-C and versican were found to correlate principally with the invasive phenotype of low-grade astrocytoma, thus these molecules can potentially serve as targets for anti-invasion therapy in the future.
肿瘤切除范围决定了术后肿瘤治疗的效果。这对于原发性脑肿瘤尤其如此,因为肿瘤周围浸润通常使根治性切除变得不可能。本研究的目的是确定不同颅内肿瘤侵袭相关分子的特定表达模式,并确定主要负责二级星形细胞瘤肿瘤周围侵袭的分子。测定了来自二级星形细胞瘤、神经鞘瘤、非小细胞肺癌脑内转移和正常脑组织的组织样本中 26 种细胞外基质 (ECM) 分子的 mRNA 表达。还对每个肿瘤组的脑蛋白聚糖、神经蛋白聚糖、腱蛋白 C 和 versican 的免疫组织化学染色进行了分析。与转移、神经鞘瘤和正常脑组织相比,星形细胞瘤和转移、神经鞘瘤与正常脑组织相比,在 mRNA 水平上分别有 22、17、20、21 和 19 种分子明显过表达。mRNA 表达的聚类分析显示出每个组织学组的特定基因表达模式。在 26 种分子中,有 4 种与星形细胞瘤相关。免疫组织化学染色在蛋白水平上证实了 mRNA 分析的结果。不同来源的肿瘤具有特定的侵袭表型,这可以在基因表达水平上明显确定。侵袭相关分子的这种特征表达模式可能有助于筛选抗侵袭药物的精确靶点。在低级别星形细胞瘤中,脑蛋白聚糖、神经蛋白聚糖、腱蛋白 C 和 versican 与低级别星形细胞瘤的侵袭表型主要相关,因此这些分子可能成为未来抗侵袭治疗的潜在靶点。