Multiple RT-PCR tyrosinase testing reveals that melanoma cells circulate in the blood of melanoma patients at the frequency more than 10 times below the detection threshold

Prognostic Value of Multiple Reverse Transcription-PCR Tyrosinase Testing for Circulating Neoplastic Cells in Malignant Melanoma

“…The extreme variability of individual TYR test results in MM has prompted several authors to question its diagnostic and prognostic value as well as its biological significance (13,17,25,28 ). Our previous (31 ) and current studies have demonstrated that testing each patient several times and then applying methods of statistical analysis to the interpretation of the results is a useful approach to this problem. Using this approach, we could demonstrate all of the phenomena classically expected from diagnostic testing, including (a) increased frequency of positive testing in more advanced disease, and (b) increased risk of relapse in patients testing positive more frequently.…”

“…It is much more difficult to interpret multiple negative results. From our previous study (31 ), it appears that Ͼ10 consecutive negative TYR tests are necessary to consider a given patient as being free of disease with a sufficient degree of confidence to provide a guarantee of the patient's safety. Although this result is supported by statistical analysis, using it as the basis for a testing procedure might create practical obstacles because it would increase the cost of testing and requires several visits on the part of the patient.…”

“…Using the second approach, we previously demonstrated that, in fact, CMCs are more often detected in more advanced melanoma than in less advanced disease (31 ). The aim of the present study was to evaluate whether this approach might be of value in predicting the prognosis of melanoma patients.…”

“…We recently provided an explanation for this variability by demonstrating that it is attributable to low concentrations of CMCs in the peripheral blood [more than 10-fold below the detection threshold of the assay (31 )]. In such a situation, the error would be so high that it would make the evaluation of prognostic significance of an individual test result meaningless.…”

The history and future of melanoma staging

“…More importantly, detection of CMCs was shown to be an indicator of early relapse and poor survival from melanoma [64,[66][67][68][70][71][72]74]. Multiple tests were shown to increase the sensitivity of detection of CMCs [ [75][76][77] and tests carried out up to 6 months after surgical removal of localized melanoma were still shown to be associated with an adverse prognosis [70]. Curry et al [75] found that tests on three blood samples taken in the first 3 months after surgical removal of melanoma provided the highest sensitivity for detection of CMCs.…”