Page 77 - Read Online

Table 2: Advantages and disadvantages of different methods for brain tumors biomarkers detection in the
CSF
Approach Method Pros Cons
CSF cytoanalysis: CSF
is examined under a Highly specific [12-14,16] Low sensitivity and false negative
microscope to look for results are common [3,13,20,23,24]
cancer cells
Flow cytometry analysis: False negative and false positive
Have the potential to Automated method that allows results can occur (especially at low
[14,25]
provide information rapid analysis cell counts, < 25 cells/uL).
Detection of cancer about cell surface protein Smaller CSF volume is needed [9,23] Poor differential ability between
cells in the CSF expression mitoses and neoplastic cells is
reported
[14,23,25]
Other tools: Measuring
chromosomal content of
cancer cells in the CSF These techniques have the ability
using DNA single cell to detect genetic aberrations as a Low sensitivity [26]
cytometry techniques sign of malignancy location [26]
or fluorescence in-situ
hybridization
CSF proteomic analysis:
Systematic identification Specific proteomic patterns can
and quantification of the differentiate subtypes or grades of Limited sensitivity and specificity [31]
complete complement of specific brain tumors [27-30]
proteins in the CSF
Detection of High specificity and chemical
biochemical molecules stability [60,101] Only small amounts
secreted by cancers to of CSF samples are required for the The unknown origin and factors
the CSF CSF microRNAs analysis: detection of miRNAs in the CSF influence their level of expression
Measuring microRNA
Profiling of CSF offers the advantage of convenient might impact their specificity as
[76,102-106]
repetitive monitoring of molecular biomarkers
events happening in cancer in the
response to treatment [76]
CSF: cerebrospinal fluid
cells in the CSF and morphological similarities between both cytology and flow cytometry were significantly higher
benign and malignant cells. [13,23,24] The lack of standardized compared with those found to be positive by flow cytometry
techniques for obtaining and evaluating CSF cytology alone. [23]
specimens and the absence of molecular analysis of tumor
cells certainly contributes to the wide sensitivity range. It has to be said that both false negative and false positive
[3]
Hence although it is currently used in the clinic, CSF results (especially at low cell counts, < 25 cells/uL) can
cytology remains a poor surrogate marker for disease occur with flow cytometry too, a poor differential ability
response in brain cancer/metastasis involvement. [9,13] between mitoses and neoplastic cells is also reported Table
2. Therefore before flow cytometry can be recommended
Flow cytometry analysis in a routine CSF examination in combination with the
CSF fluid flow cytometry is a useful addition to CSF conventional cytology, standardized protocols are needed
cytology. Cytology examines morphologic patterns, and to uniform definitions of positivity and procedure. [14,23,25]
flow cytometry has the potential to provide information Rare cell capture technology, for example, CellSearch is
®
about cell surface protein expression. It is an additional a recent technique using molecular markers to detect and
highly sensitive cytological technique capable of accurately enumerate circulating tumor cells in the CSF. This method is
detecting malignant CSF cells, especially in comparatively established to detect prognostic marker on different cancer
smaller CSF volume and in samples with very low cell cells circulating in the peripheral blood such as breast
counts when combined with multicolor fluorescent antibody cancer and has recently attracted the interest of CSF cancer
labelling. [9,23] In this method CSF must be processed researcher. [3,9] However, the application of CellSearch
®
similar to cytology within 1 hour of sampling however technology for detecting primary CNS cancer cells in CSF
centrifugation should be minimized. [14,23] Automated has not been published yet.
methods allow rapid flow cytometry data analysis and
thereby reduce the significant time expenditures used in Other tools for cancer cell detection in the CSF
conventional cytology routine. [14,25] Flow cytometry seems Measuring the chromosomal content of cancer cells in
to provide a higher sensitivity. However the cell count and the CSF, using DNA single cell cytometry techniques
the percentage of neoplastic cells reported in the CSF by or fluorescence in-situ hybridization that detects genetic

178
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ May 18, 2016 ¦