gms | German Medical Science

Objective: Gliomas are the most common primary human brain tumors which consist of a heterogeneous group of benign and malignant neoplasms that are histologically classified according to the World Health Organization into four groups (WHO grade I-IV). Metals are vital components of life. An estimated one-third of all proteins require metal ions as cofactors for protein function. The homeostasis of metal ions is essential for many biological activities. We used synchrotron x-ray fluorescence (XRF) imaging to assess the element profiles and metal imbalance distribution in cells and tissues originating from different grades of brain tumors.

Method: Seven tumor specimens of different malignancy grades (4 tissues and 3 stem-like cancer cell (SLCC) cultures) are assessed by synchrotron micro-XRF. Ten μm thin sections of dried and frozen tissues were used for the analysis. Samples were attached on the silicon-nitride holders. The scanning area was 30x30 μm (SLCC) and 50x50 μm (tissues). The x-ray energy was set to 9.7 keV, exposure time was 100 ms. The following elements were detected: P, S, Cl, K, Ca, Fe, Co. The net peak areas of K-α lines were used for the quantitative evaluation of elements. Evaluation of XRF spectra was performed by using the Pymca software.

Results: The distribution map for each element showed that the single elements in tumor tissues of lower malignancy grades are more homogeneously distributed than in higher grade tumors. The analysis of peak area showed that the strongest difference is in the K, Cl and Ca concentration. In the frozen tissue sample group, glioblastoma (GBM, WHO grade IV) shows the highest heterogeneity in the distribution for all analyzed elements and the highest concentration for P, S, Zn. The highest concentrations of Ca and K were detected in one of the GBM samples. In dried tissues, the most heterogeneously distributed elements are P, S, Cl, K, Fe and Co.

Conclusions: Large heterogeneity in the elemental distribution and concentration was observed in GBM, which raises the question of whether heterogeneities are due to the changes in histological architecture of the sample or due to the different molecular alternation. More homogeneity in element distribution in lower grade gliomas is probably due to the presence of healthy tissue. For statistical improvement more samples analysis is required. Next step will include more detailed trace metal analysis, as the XRF is an ideal method for their in situ mapping.