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Melanoma: Circulating Tumor Cells Found to Indicate Metastasis, but Implications Unclear

Susman, Ed

doi: 10.1097/

NEW ORLEANS—The presence of circulating tumor cells (CTCs) in patients being treated for melanoma appears to indicate a poorer prognosis, Italian researchers reported here at the American Academy of Dermatology Annual Meeting.

In a study aimed at devising new ways of quantifying melanoma circulating tumor cells, Marta Grazzini, MD, Assistant Professor of Medicine at the University of Florence, said that the tumor cells in the blood were found only in patients with primary invasive melanoma and in patients with metastatic melanoma.

Among the 38 healthy volunteers, no CTCs were found, Dr. Grazzini said in her oral poster discussion. Similarly, no CTCs were identified in the blood of five patients with non-melanoma skin tumors or in the 10 patients diagnosed with in situ melanoma who were undergoing surgery for melanocytic nevi (in situ melanoma was defined as a Breslow depth of 0).

However, among 62 patients diagnosed with primary invasive melanoma, CTCs were observed in 18 patients—about 29%. Circulating tumor cells were also identified in five of eight patients with metastatic disease.

“Circulating tumor cell detection corroborated by suitable molecular characterization may assist in the identification and monitoring of more appropriate therapies in melanoma patients,” Dr. Grazzini said.

Exactly what role the identification of CTCs will play in clinical therapy remains controversial, noted the moderator of the poster discussion session, Shasa Hu, MD, Assistant Professor of Dermatology at the University of Miami Miller School of Medicine.

“There are a lot of new studies on stem cells in melanoma and circulating tumor cells, and we have yet to define the clinical significance of these cells as well as their influence on treatment. It is too early in the research to speculate on what a clinician should do if circulating tumor cells are identified.

“Circulating tumor cells actually are now studied just in research centers. We don't want to push for their use in patients until we have better data. We don't know at this point whether treatment based on circulating tumor cells will have any impact on outcomes….The prognosis for thin melanoma is excellent, so if we have circulating tumor cells in patients with thin melanoma what does it really mean?”

Dr. Grazzini also acknowledged the uncertainty: “The clinical relevance of our finding is still under scrutiny, and the biological fate of circulating melanoma cells must be carefully investigated.”

Indeed, she noted in her presentation, just being able to identify circulating tumor cells was a difficult task. “The majority of circulating tumor cell detection methods available to date are based upon immune-afinity and density gradient centrifugation enrichment procedures using antibodies against surface antigens. In cutaneous melanoma patients, circulating tumor cells have been studied mostly by means of real time-polymerase chain reaction [RT-PCR].”

But that procedure has limitations, Dr. Grazzini said. “Cell integrity is lost during RNA extraction, thus preventing the analysis of cell morphology and phenotype. RT-PCR allows neither cell counting nor demonstration of tumor microemboli, which are considered to have a major role in the metastatic process.”

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Hence, Dr. Grazzini and her colleagues set out to develop other tools for identifying circulating tumor cells in the blood. One of the new technologies that the research team explored is known as ISET (isolation by size of epithelial tumor cells). She noted that use of this technology—a sophisticated filtration system—provides a direct method for identification of CTCs.

“The tumor cells can be collected by filtration because of their large size in comparison with peripheral blood leucocytes,” she explained. To assess whether the techniques could be used in patients, the researchers tested the blood of both cancer patients and health volunteers.”

The researchers took a sample of a patient's blood right after surgery and then two months later. The second blood collection was taken in case the first sample was contaminated by cells that escaped into the blood during the surgical procedure.

The identification of the cells trapped in the filters as circulating tumor cells was supported by positive immunohistochemical markets and RT-PCR, Dr. Grazzini said. “Circulating tumor cell detection correlated with the presence of mRNA tyrosinase in blood samples, assayed by RT-PCR.”

She illustrated various slides that showed the large size of the tumor cells compared with other cells in the blood. When stained using immunohistochemical analyses, these larger cells proved consistent with melanoma cells.

In response to questions from the audience, Dr. Grazzini said the results also correlated with Breslow depth—the greater the Breslow depth, the more likely it was to detect CTCs.

© 2011 Lippincott Williams & Wilkins, Inc.
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