Spoilt for Choice: Therapy Decisions for Skin Cancer Patients

To select the optimal therapeutic strategy for malignant melanoma, the most serious form of skin cancer, it is crucial to be able to discriminate, with high reliability, tumor stages and chances of recurrence with the aid of tumor markers and to predict disease progression on this basis. In collaboration with several working groups based in Nottingham, England, Professor Dirk Schadendorf, head of the Clinical Cooperation Unit “Dermato-Oncology” of the German Cancer Research Center, Heidelberg (Deutsches Krebsforschungszentrum, DKFZ) and his co-worker, Dr. Selma Ugurel, have investigated a method for identifying stage-specific tumor markers. In the Journal of Clinical Oncology the scientists present the benefits of their method which combines a form of mass spectroscopy with bioinformatic algorithms.

So far, there have only been few tumor markers available for predicting disease progression in melanoma. S100-â, a molecule that can be identified by immune staining, is often used as an indicator of advanced, metastasizing cancer. The Heidelberg researchers, jointly with colleagues from the U.K., have now tested a new approach: They generated profiles of all proteins in blood serum samples of 205 melanoma patients in stages I and IV. Using MALDI-ToF (Matrix Assisted Laser Desorption/Ionisation-Time of Flight) mass spectroscopy, the investigators found out that patients with advanced disease (stage IV melanoma) have a characteristic protein pattern that is clearly different from the profiles of stage I patients. These results were combined with an analytical software called artificial neuronal network (ANN).

After a “learning process”, ANN was able to systematically distinguish stage I patients from stage IV patients based on the tumor markers. In analogy to this, it became possible to predict the chance of recurrence in stage III patients after surgical removal of the primary and secondary tumors. Predictions based on the combination of MALDI-ToF and ANN turned out to be reliable in 82 percent of cases, while S100-â facilitated correct differentiation in only 21 percent of cases. If the procedure proves its worth, protein profiles may in future contribute to identifying high-risk patients and referring them to adjuvant therapy more rapidly .

In Germany, approximately 11,400 people – about 6,100 women and 5,300 men – are diagnosed with malignant melanoma each year. Malignant melanoma thus accounts for almost three percent of all malignant neoplasias and causes about one percent of all cancer deaths (in 2000: 1,017 women and 1,161 men).

*Shahid Mian, Selma Ugurel et al.: “Serum proteomic fingerprinting discriminates between clinical stages and predicts disease progression in melanoma patients“, Journal of Clinical Oncology, Aug 1, 2005; 23 (22)