Serologic and immunohistochemical prognostic biomarkers of cutaneous malignancies

Biomarkers are important tools in clinical diagnosis and prognostic classification of various cutaneous malignancies. Besides clinical and histopathological aspects (e.g. anatomic site and type of the primary tumour, tumour size and invasion depth, ulceration, vascular invasion), an increasing variety of molecular markers have been identified, providing the possibility of a more detailed diagnostic and prognostic subgrouping of tumour entities, up to even changing existing classification systems. Recently published gene expression or proteomic profiling data relate to new marker molecules involved in skin cancer pathogenesis, which may, after validation by suitable studies, represent future prognostic or predictive biomarkers in cutaneous malignancies. We, here, give an overview on currently known serologic and newer immunohistochemical biomarker molecules in the most common cutaneous malignancies, malignant melanoma, squamous cell carcinoma and cutaneous lymphoma, particularly emphasizing their prognostic and predictive significance

Melanoma progression and serum L-dopa/L-tyrosine ratio: a comparison with S100B.

The challenge to find a reliable tumour marker for the management of melanoma patients still remains. In this study, the serum L-dopa/L-tyrosine ratio was compared with serum S100B as a reference marker. A total of 89 melanoma patients were sampled and staged according to the American Joint Committee on Cancer (AJCC) classification. Of these, 19 stage III and 28 stage IV patients were evaluated for disease progression at 1.5 years and 6 months post-sampling, respectively. Serum L-dopa and L-tyrosine were measured by high performance liquid chromatography (HPLC) (normal value for ratio < 16 x 10(-5)) and S100B using the LIA-mat Sangtec 100 assay (normal value < 0.10 microg/l). Non-parametric tests (Kruskal-Wallis analysis of variance, Dunn's and Spearman) were used for the statistical analysis. The median serum L-dopa/L-tyrosine ratio was 16.0 x 10(-5) (range 2.7-545.1 x 10-5 and the median S100B level was 0.15 microg/l (range < 0.10-13.8 microg/l), with a sensitivity of 51% for the ratio and 66% for S100B. There was a 47% discordance and no correlation between the two markers (r = 0.149). The ratio was higher in stage IV than in other stages (P < 0.05), as was the S100B level (P < 0.0001). Both markers were higher in patients with evolutive disease (n = 23) than in stable patients (n = 24), with values of 20.8 x 10(-5) versus 13.1 x 10(-5) for the ratio (P < 0.05) and 0.89 microg/l versus 0.16 microg/l for S100B (P < 0.001); for the ratio, this difference was more pronounced in stage III than in stage IV patients. The overall sensitivity and specificity of the markers to predict disease progression were 78% and 67%, respectively, for the ratio, and 74% and 83%, respectively, for S100B (using an ROC cut-off of 0.38 microg/l). In conclusion, the serum L-dopa/L-tyrosine ratio correlates with melanoma progression and has predictive value, especially in stage III patients. This tumour marker, like S100B, could serve as an additional tool in the management of melanoma.Comparative StudyEvaluation StudiesJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Evaluation of the serum L-dopa/L-tyrosine ratio as a melanoma marker.

A wide range of molecules have been investigated as tumour markers in melanoma, most of which are not suitable for use by clinical oncologists for the detection of fast and unpredictable metastatic dissemination. We have already shown that the serum L-dopa/L-tyrosine ratio (an index of tyrosinase functional activity) correlates with the tumour burden and in some cases predicted disease progression in metastatic melanoma patients. We examined the potential value of this ratio for the follow-up, therapy monitoring and prognosis in melanoma compared with a reference marker (S100B, a melanoma-associated antigen). Sixty melanoma patients (24 stage I-II, 18 stage III, 18 stage IV, American Joint Committee on Cancer staging) were entered into the study, sampled two to eight times (before and after therapy) and were followed for up to 30 months. Serum L-dopa and L-tyrosine were determined by high performance liquid chromatography and S100B by an immunoluminometric assay. In stage III patients with elevated marker concentration, lymph node dissection decreased the S100B level (from 0.27 to < 0.13 microg/l, P=0.008), but not the L-dopa/L-tyrosine ratio. Chemotherapy decreased the L-dopa/L-tyrosine ratio by 38% (P =0.04) and the S100B level by 45% (P = 0.02) in stage IV responders. During follow-up, patients with marker levels within normal limits (n=19) had stable disease, except for two stage II patients. In patients with progressive disease (n=20), an increase in one or both markers was observed. Stage IV patients with high L-Dopa/L-Tyrosine ratio (above 20 x 10-5) at inclusion had shorter survival (3 months), while patients with low levels had longer survival (15 months). Levels of S100B had no impact on survival, as all stage IV patients (with levels below or above 0.38 microg/l) had the same survival (5 months). The serum L-dopa/L-tyrosine ratio may be influenced by successful therapy and levels at inclusion may correlate with prognosis in stage IV patients. Levels of these two markers in other biological fluids such as cerebrospinal fluid and tumour exudates may be useful diagnostically and prognostically in difficult cases.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial.

Individuals affected by melanoma with thick primary tumours or regional node involvement have a poor outlook, with only 30-50% alive at 5 years. High-dose and low-dose interferon alfa have been assessed for the treatment of these patients, with the former having considerable toxicity and a consistent effect on disease free survival, but not on overall survival, and the latter no consistent effect on either. Our aim was, therefore, to assess the effect of two regimens of interferon of intermediate dose versus observation alone on distant metastasis-free interval (DMFI) and overall survival in such patients.Clinical TrialJournal ArticleMulticenter StudyRandomized Controlled TrialResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prognostic value of serial blood S100B determinations in stage IIB-III melanoma patients: a corollary study to EORTC trial 18952.

S100B is a prognostic factor for melanoma as elevated levels correlate with disease progression and poor outcome. We determined its prognostic value based on updated information using serial determinations in stage IIb/III melanoma patients. 211 Patients who participated in the EORTC 18952 trial, evaluating efficacy of adjuvant intermediate doses of interferon α2b (IFN) versus observation, entered a corollary study. Over a period of 36 months, 918 serum samples were collected. The Cox time-dependent model was used to assess prognostic value of the latest (most recent) S100B determination. At first measurement, 178 patients had S100B values <0.2 μg/l and 33 ≥ 0.2 μg/l. Within the first group, 61 patients had, later on, an increased value of S100B (≥ 0.2 μg/l). An initial increased value of S100B, or during follow-up, was associated with worse distant metastasis-free survival (DMFS); hazard ratio (HR) of S100B ≥ 0.2 versus S100B < 0.2 was 5.57 (95% confidence interval (CI) 3.81-8.16), P < 0.0001, after adjustment for stage, number of lymph nodes and sex. In stage IIb patients, the HR adjusted for sex was 2.14 (95% CI 0.71, 6.42), whereas in stage III, the HR adjusted for stage, number of lymph nodes and sex was 6.76 (95% CI 4.50-10.16). Similar results were observed regarding overall survival (OS). Serial determination of S100B in stage IIb-III melanoma is a strong independent prognostic marker, even stronger compared to stage and number of positive lymph nodes. The prognostic impact of S100B ≥ 0.2 μg/l is more pronounced in stage III disease compared with stage IIb.Clinical Trial, Phase IIIJournal ArticleRandomized Controlled TrialResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe