Circulating melanoma cells as a potential biomarker to detect metastasis and evaluate prognosis

Abstract

TNM staging is mainly used to evaluate the prognosis of melanoma patients. Serum biomarkers such as 5-S-cysteinyldopa (5-S-CD) have occasionally been used but most do not respond until the tumour burden becomes high. Recently, circulating melanoma cells (CMC) have been reported as a possible new biomarker to detect metastasis, monitor treatment response and predict prognosis. The object of this exploratory study was to evaluate the efficacy of CMC to detect metastasis and predict prognosis by cross-sectional and prospective observational analyses, respectively. Altogether 15 patients with stages II-IV melanoma were enrolled and CMC were enumerated by CellSearch system with cut-off values of two cells/7.5 mL. Serum 5-S-CD and lactate dehydrogenase (LDH) were also measured. The sensitivity of CMC and 5-S-CD for the detection of metastasis was 33 and 50%, respectively. The combination of CMC and 5-S-CD showed a sensitivity of 67%, the best performance among CMC, 5-S-CD, LDH and any combination of two of the markers. Additionally, a 30-month prospective observation showed that CMC could segregate patients with poorer prognosis. The median survival time for the patients with <2 CMC and those with ≥2 CMC was 19.5 and 4.5 months, respectively. The limitation of this study is the small sample size. These preliminary results indicate CMC may complement the efficacy of 5-S-CD to detect metastasis and can be a prognostic marker. Although there is still room for improvement to maximise the sensitivity, the CellSearch system is reproducible, standardised and suitable for multi-centre studies.

Liquid biopsy to monitor melanoma patients

“…Only cells positive for MCAM, DAPI and HMW‐MAA and negative for CD34 and CD45 are considered to be melanoma cells. In 26–33 % of patients with metastatic melanoma, the CellSearch™ system detected more than two viable cells per 7.5 ml of blood, thereby segregating patients with a poor prognosis . However, not all melanomas express MCAM and HMW‐MAA, and benign lesions that express HMW‐MAA or MCAM exist .…”

Liquid Biopsy zur Überwachung von Melanompatienten

“…Nur Zellen, die positiv für MCAM, DAPI und HMW‐MAA und negativ für CD34 und CD45 sind, werden als Melanomzellen betrachtet. Bei 26–33 % der Patienten mit metastasiertem Melanom wurden mit dem CellSearch™‐System mehr als zwei lebende Zellen pro 7,5 ml Blut gefunden, wobei dies mit einer ungünstigen Prognose verbunden war . Allerdings exprimieren nicht alle Melanome MCAM und HMW‐MAA, und benigne Läsionen können ebenfalls HMW‐MAA oder MCAM exprimieren .…”

Improving the CellSearch® system

“…The CellSearch test used for the FDA clearance has also been tested in many other cancers [15], and the presence of CTC is also associated with poor clinical outcome in gastric cancer [16,17], small-cell lung cancer [18][19][20], melanoma [21,22], endometrial cancer [23], esophageal squamous-cell carcinoma [24,25], cholangiocarcinoma [26], colon cancer, liver metastasis [27], hepatocellular carcinoma [28], pancreatic cancer [29], rectal cancer [30], bladder cancer [31], head and neck cancer [32], and ovarian cancer [33]. Publications referred to above are just examples.…”

“…The melanoma cells are identified as nucleated cells that express the high-molecular-weight melanoma-associated antigen and lack CD45 and CD34 [22]. Circulating melanoma cells identified in this manner also associate with poor clinical outcome [21,22,[41][42][43].…”