Long Term Survival Of Stage II And III Melanoma Patients With Respect To Serial Tyrosinase RT-PCR Testing In Peripheral Blood

Reviewer: Heather Jones, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 22, 2002

Presenter: Christiane A Voit
Presenter's Affiliation: University of Mainz, Mainz, Germany
Type of Session: Scientific


    Melanoma has a high metastatic potential even in small primary lesions, and an early distinction between localized and regionally/distally advanced disease is of major importance for the patients' treatment and, consequently, for their survival. Exploiting the fact that tyrosinase is a tissue specific enzyme, which is only expressed in normal skin melanocytes and malignant melanoma, one can use reverse transcriptase polymerase chain reaction to attempt to detect cells that invade the blood during metastases. We know that the detection of micrometastatic melanoma cells with sentinel lymph node biopsy has proved to be a very important prognostic marker for survival. Whether early detection of circulating melanoma cells in peripheral blood has similar consequences is the study question in this investigation.

Materials and Methods

  • 100 patients were enrolled in the study
  • N=66 stage II and N=34 stage III (AJCC) melanoma patients received serial testing for tyrosinase transcripts in peripheral blood
  • A total of 248 blood samples were analyzed during the test interval of 2 years using a reverse transcriptase polymerase chain reaction (RT-PCR) assay.
  • Median follow-up time from the first blood sample was 3.5 years (range 0.9-5.4).
  • The disease-specific survival time was calculated as time from first blood sampling to the time of death from melanoma


  • The 4-year disease-specific survival probability was 97% for patients always showing negative RT-PCR results and 69% for patients tested at least once positive.
  • A Cox proportional hazard model revealed that sex, site of the primary tumor, histological subtype, Breslow tumor thickness, and the time dependent variable PCR outcome were important prognostic factors.
  • Patients with a positive RT-PCR test were at a higher risk of death from melanoma with a hazard ratio of 48.7 (95% confidence interval 5.0 - 474.0, p < 0.001)

Author's Conclusions

    This study showed a strong association between RT-PCR detected melanoma cells and poor disease specific survival time. Detection of circulating tumor cells in peripheral blood of melanoma patients might have similar impact on the course of melanoma disease as detection of micrometastatic disease with sentinel lymph node biopsy. A combination of these two methods may be useful and lead to a better prognosis for melanoma patients thus; this combination should be studied further.

Clinical/Scientific Implications

    RT-PCR appears at present to be a reliable and reproducible method for the detection of low-level disease in cancer patients, although prospective phase IIII studies are warranted to assess the clinical utility of different molecular diagnostic methods. Preliminary results of this study suggest that the method is sensitive and specific to the circulating melanoma cells detection in the peripheral blood and may thus be helpful in determining the disease stage and, consequently, in planning treatment. We await further studies that seek to combine the detection of micrometastasis in both the sentinel nodes and peripheral blood

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