fThe need to investigate the lymph node is crucial in melanoma, as patients whose cancer has advanced need supplementary treatment beyond simple excision, and late-stage melanoma is very aggressive. Fraunhofer’s approach to lymph node analysis using the Parsortix system improves the process while also reducing costs.
Key areas of investigation for melanoma—and for several other cancers, including head and neck cancer and lung cancer—are to determine whether the cancer has spread to the lymph nodes, and to determine the stage of the cancer in order to inform treatment decisions. Standard clinical practice is to resect the sentinel lymph node nearest to the melanoma. The lymph node is then processed to create a formalin-fixed paraffin-embedded (FFPE) tissue block, from which slices are sectioned and stained for use as a tissue biopsy. The stained slices are then examined for the presence of metastasis or single disseminated tumor cells. If tumor cells are found, the patient is identified as Stage 3 and will be given chemotherapy in addition to having the melanoma excised.
However, there are a number of known problems with the current approach, which Fraunhofer has addressed by using the Parsortix system to harvest disseminated tumor cells from lymph node material. Key issues addressed by Fraunhofer include the following.
- The lymph node may contain very few disseminated tumor cells, and examination of FFPE samples only investigates a small proportion of the tissue. Consequently, Fraunhofer believes, disseminated tumor cells may be missed in up to 50% of patients, who are then likely to be incorrectly staged. This outcome can be improved by mechanical disaggregation of the lymph node to a single-cell suspension, allowing analysis of the entire lymph node.
- Microscopic evaluation of such a single-cell suspension requires multiple microscope slides and is time-consuming and expensive in terms of laboratory technician time. The Parsortix system can process the entire lymph node, harvesting all the disseminated tumor cells that may be present, and reducing the number of false negatives. This process greatly enriches the disseminated tumor cells so that only one microscope slide is needed.
- Unless there are many disseminated tumor cells present, it can be difficult to use FFPE tissue samples to undertake molecular analysis for detecting the presence of the protooncogene BRAF or other molecular markers. As a consequence, patients who are BRAF-positive in their lymph node disseminated tumor cells may not receive appropriately targeted treatment. The Parsortix system provides the disseminated tumor cells in a form that supports molecular analysis, not just for BRAF but for other relevant genes as well.
“The new approach using the Parsortix system streamlines the analysis of lymph nodes in melanoma for a higher sensitivity of detecting the spread of cancer to the lymph node and greatly improving the ability to undertake key molecular analysis on the cancer,” explains Bernhard Polzer, group leader for molecular diagnostics at the Fraunhofer institute. “It is an added benefit that it also facilitates single-cell analysis, reducing costs. We previously tried other circulating tumor cell systems, including antibody-based and membrane systems, but these were not suitable for this process.”
“This is another example of our leveraged approach, with research customers delivering new applications for Parsortix,” says Andrew Newland, founder and chief executive of Angle. “There is now the potential for the Parsortix system to be adopted as a standard approach for analyzing lymph nodes, which is a requirement for all patients diagnosed with melanoma and several other cancer types.”
For further information, visit Angle plc.
Featured Image: The Parsortix PC1 clinical system is being used to harvest circulating tumor cells in FDA clearance studies at MD Anderson and other leading US cancer centers.
- Weidele K, Stojanovic N, Feliciello G, et al. Microfluidic enrichment, isolation, and characterization of disseminated melanoma cells from lymph node samples. Int J Cancer. Epub ahead of print, December 26, 2018; doi: 10.1002/ijc.32092.