Screening for genetic markers in the blood of melanoma patients could improve chances of survival
Scientists have discovered the tumour cells which make melanoma patients more likely to have their cancer spread or come back following treatment, according to a study published in the British Journal of Dermatology.
A team of researchers in Western Australia and Boston in the U.S. looked at the role of melanoma cells circulating in the blood of patients who had already been diagnosed with the disease, and how these cells relate to recurrence of the disease and treatment efficacy. The aim of the research was to identify those subgroups of patients who are more likely to suffer disease recurrence or poor treatment outcomes, in order to provide them with more targeted treatments at an earlier stage, which could improve survival rates.
The study was the first to measure not only the presence of less aggressive cancer cells spread by melanoma tumours into the bloodstream, but also the presence of the destructive minority of cancer ‘stem’ cells, which represent the driving force behind the growth of tumours. To do this, blood was collected from 230 patients with both primary melanoma (where it has not spread) and metastatic melanoma (spreading to other parts of the body), and compared with the blood of 152 healthy controls.
The researchers found that the presence of tumour cells in a person’s blood alone does not necessarily correlate with disease spread or recurrence, as these cells can still be present even when a patient is considered clinically disease free. It is in fact the behaviour and characteristics (phenotype) of these cells that is particularly important.
Therefore, a test for the different genes produced by tumour cells was used to identify those patients more likely to have their cancer spread or come back following treatment. The researchers looked at five different ‘genetic markers’, which are genes or pieces of DNA that allow scientists to tell what different cells are doing. These markers are all found in melanoma tumour cells, of which there are many different types.
The presence and level of different genetic markers in the blood was shown to be useful in assessing a patient’s disease spread, response to treatment, and risk of relapse.
The results revealed increased levels of one gene, called the MCAM marker, correlated with patients whose melanoma had spread to other parts of the body. The link between MCAM genes and a poor response to therapy was also confirmed in the findings, with higher levels of MCAM seen in patients whose treatment had been unsuccessful. 40 of the 62 patients with late stage (IV) melanoma in the study had a negative treatment outcome (progression and/or death); 43% of this subgroup expressed the MCAM marker in their blood.
Lead author of the study, Dr Ziman of the Edith Cowan University, Perth, said: “Patients with metastatic (spreading) melanoma have, to date, shown a poor response rate to conventional treatments. MCAM expression could now be used to monitor treatment resistance, and help to identify a subset of patients who may benefit from an alternative treatment regime.”
The scientists also looked at recurrence of the disease, and were able to identify that two markers called MLANA and ABCB5 were linked with relapse. In the 73 patients who had a relapse, these markers were found to be expressed considerably more frequently (45% and 49% respectively) than in patients without recurrence (23% and 34% respectively). Therefore, the specific detection of ABCB5 and MLANA expressing tumour cells in a patient’s blood could be a valuable predictor of clinical outcome and disease recurrence. The ABCB5 gene marks a subset of rare, chemotherapy-resistant melanoma stem cells.
Another of the study’s authors, Markus Frank, Assistant Professor of Paediatrics and Dermatology at the Harvard Medical School, said: “This has very important implications for melanoma patients. The development of a minimally invasive method of measuring the frequency of melanoma cells, and melanoma stem cells in particular, can be used to follow patient responses to current or novel and emerging melanoma therapies. In turn this will help determine if a particular therapy is capable of eliminating the aggressive cancer stem cell population required for the complete eradication of the cancer, potentially achieving a cure.”
Melanoma is the deadliest form of skin cancer, which is the most common cancer type in the UK. There are approximately 13,000 new cases of melanoma diagnosed every year in the UK and 2,300 deaths.
Kimberley Carter of the British Association of Dermatologists said: “Melanoma has a high potential to spread and patients who develop distant metastases, where the cancer spreads to remote parts or organs of the body, currently only have a ten year survival rate of 16 per cent. Therefore, studies like this one which look to find methods of detecting melanoma spread at early stages are critical to care of melanoma patients. Research of this kind will hopefully help to deliver more accurate and targeted treatments to melanoma patients in the future, especially those who have not responded well to first-line treatments.”
Five genetic markers in the patients’ blood were examined: MLANA, PAX3d, TGFβ2, MCAM and ABCB5. MLANA and PAX3d are both expressed by melanocyte cells, TGFβ2 and MCAM are both tumour cell markers, and ABCB5 is a stem cell marker. MCAM is a known marker of melanoma tumour progression.
Notes to editors:
1. If using this information, please ensure you mention that the study is being released in the British Journal of Dermatology, the official publication of the British Association of Dermatologists
For more information please contact: Kimberley Carter, British Association of Dermatologists, Phone: 0207 391 6084, Email: firstname.lastname@example.org, Website: www.bad.org.uk
2. Articles in the BJD can be viewed online: www.brjdermatol.org
British Journal of Dermatology: Markers of circulating tumour cell in the peripheral blood of melanoma patients correlates with disease recurrence and progression.
A.L. Reid1 M. Millward2, R. Pearce1, M.Lee2, M.H. Frank3, A. Ireland2, L. Monshizadeh2, T. Rai1 and M. Ziman14
1. School of Medical Sciences, Edith Cowan University, Perth, WA, Australia
2. Department of Medicine and 4. School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Australia
3. Transplantation Research Center, Children’s Hospital Boston and Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, U.S.A
Accepted for publication 14 September 2012
The British Association of Dermatologists is the central association of practising UK dermatologists. Our aim is to continually improve the treatment and understanding of skin disease.
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