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Risk-Adapted Aftercare Of Melanoma Patients. Sequence Of Tyrosinase Rt-Pcr, Ultrasound And Fine Needle Aspiration Cytology

ONKOLOGE(2007)

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摘要
Risk-adapted aftercare and adjuvant therapy of melanoma patients are still undergoing research. The most common sites of metastases are the regional lymph nodes. However, at present for a staging by the initial diagnosis of a melanoma with a thickness of >= 1 mm, only the sentinel lymph nodes are removed. in the case of apparent distant metastases (stage IV according to the AJCC), most patients will only be expected to survive for months or at best a few years, because neither chemotherapy, chemo-immunotherapy nor vaccine therapy have been reliably effective. Therefore, attempts are being made to identify markers of a minimal residual disease, with the help of which a risk-collective can be identified so that diagnostic and surgical measures can be implemented as early as possible.One of these markers is tyrosinase which is an enzyme involved in melanin synthesis. It is normally not detectable in blood, but its presence can be suggested by minimal amounts of mRNA by RT-PCR. In this study the authors have serially tested for tyrosinase in addition to the routine tumour follow-up but only in patients classified as AJCC stages II and III. These patients have a particularly high risk for distant metastases due to the size of the tumour or lymph node involvement. The patients were observed on average for 6 years. A total of 28.2% of the blood samples were positive for tyrosinase (23% stage II patients and 38.5% stage III patients). The 6-year recurrence free survival probability in patients with continuously negative RTPCR results was higher than in patients with at least one positive RT-PCR (72% versus 52%; p=0.025). This was also true for the disease-specific survival, where the 6-year survival probability in patients with tyrosinase RTPCR always negative was higher than in patients with at least one positive RT-PCR (97% versus 67%; p=0.001). Of those patients who died during the follow-up, 85% showed at least one positive RT-PCR result. RT-PCR testing was used as a time-dependent prognostic factor in a proportional hazards model. RTPCR was a prognostically relevant factor for disease specific survival with a hazard ratio of 15.8 (95% Cl 5.2-49.0; p<0.001). It was also a prognostically relevant factor for recurrence free survival with a hazard ratio of 4.5 (95% Cl 2.4; 8.5; p<0.001). Detection of tyrosinase can, therefore, give important prognostic information on the course of individual diseases in a similar way as the sentinel node status.
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关键词
melanoma patients, distant metastases, tyrosinase, melanin synthesis
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