Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss,genomic instability,and angiogenic gene expression

Background

The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs).

Methods

The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays.

Results

Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2.

Conclusion

In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.     

Co-polysomy of chromosome 1q and 19p predicts worse prognosis in 1p/19q codeleted oligodendroglial tumors: FISH analysis of 148 consecutive cases

Background

This study aimed to evaluate the prognostic significance of co-polsomy of chromosome 1q and 19p in 1p/19q codeleted oligodendroglial tumors (ODGs).

Methods

In a series of 148 ODGs with 1p/19q deletion, co-polysomy of 1q and 19p was detected by fluorescence in situ hybridization (FISH). Log-rank analysis and Cox regression methods were used to compare Kaplan–Meier plots and identify factors associated with worse prognosis.

Results

There were 104 (70.3%) low-grade ODGs and 44 (29.7%) high-grade ODGs. Co-polysomy was independently associated with shorter progression-free survival and overall survival in 1p/19q codeleted ODGs, irrespective of tumor grades. The odds ratio of without and with co-polysomy was 0.263 (95% confidence interval [CI], 0.089–0.771; P = .015) for progression-free survival and 0.213 (95% CI, 0.060–0.756; P = .017) for overall survival. Subgroup analysis confirmed this trend in both low-grade and high-grade ODGs, although the P value for high-grade ODGs was marginally significant.

Conclusions

Co-polysomy of 1q and 19p could be used as a marker to independently predict worse prognoses and guide individual therapy in 1p/19q codeleted ODGs.     

少突胶质细胞肿瘤1p/19q联合缺失与p53、10号染色体上磷酸酶及张力蛋白同源物和6-甲基鸟嘌呤-DNA甲基转移酶蛋白表达的关系

目的 探讨少突胶质细胞肿瘤染色体1p/19q联合缺失及其与p53、10号染色体上磷酸酶及张力蛋白同源物( PTEN)和O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)蛋白表达的关系.方法 收集少突胶质细胞肿瘤标本68例,其中WHO-Ⅱ级少突胶质细胞瘤42例,WHO-Ⅲ级间变性少突胶质细胞瘤26例.采用荧光原位杂交(FISH)方法分析肿瘤组织中1p/19q缺失状态；采用免疫组织化学方法对肿瘤组织中p53、PTEN和MGMT蛋白表达进行半定量分析,并进一步分析其与1p/19q联合缺失的相关性.结果 68例少突胶质细胞肿瘤中,染色体1 p、19q缺失率及1p/19q联合缺失率分别为67.65％ (46/68)、61.76％( 42/68)、57.35％(39/68).1p/19q联合缺失率在Ⅱ级和Ⅲ级少突胶质细胞肿瘤之间,差异无统计学意义(P＞0.05).1p/19q联合缺失在额叶肿瘤的发生率(76.67％,23/30)明显高于颞叶(45.00％,9/20)及其他部位肿瘤(38.89％,7/18),差异有统计学意义(P＜0.05).tp/19q联合缺失与患者性别及发病年龄无明显相关(P＞0.05).p53和MGMT蛋白表达与肿瘤分级呈正相关,而PTEN表达与肿瘤分级呈负相关,差异均有统计学意义(P＜0.05).1p/19q联合缺失与p53和MGMT蛋白低表达相关(P＜0.05),而与PTEN蛋白表达无明显相关(P＞0.05).结论 在少突胶质细胞肿瘤中,染色体1p/19q联合缺失与p53和MGMT蛋白表达水平呈负相关.