An unexpected inverse correlation between soluble epidermal growth factor receptor and interleukin-6 in metastatic malignant melanoma patients.

The exact role of the soluble form of epidermal growth factor receptor (sEGF-R) in melanoma disease remains to be determined. We focused this study on the detection of circulating levels of sEGF-R in metastatic malignant melanoma patients and on the possible relationship between sEGF-R and clinicobiological parameters including circulating interleukin-6 (IL-6) and survival. sEGF-R and IL-6 levels were determined using a highly sensitive enzyme-linked immunosorbent assay in serum from 75 metastatic malignant melanoma patients and 30 healthy controls. In our patients, median sEGF-R level was significantly elevated (P < 0.0001) compared with that of healthy controls (173.4 vs. 91.9 fm/ml). Age or sex was not associated with sEGF-R levels. Regarding tumor burden, in contrary to the detected IL-6 levels, we found that median sEGF-R levels were significantly (P = 0.045) lower in patients with high tumor burden (163 fm/ml) than in those with low tumor burden (193.8 fm/ml). An inverse correlation between IL-6 levels and sEGF-R was observed (r =-0.33; P = 0.040). No relationship between sEGF-R and time to progression or overall survival was observed while circulating IL-6 was found as a predictive factor of survival. Our results showed that sEGF-R level was elevated in metastatic malignant melanoma patients but not related to time to progression or survival and demonstrated an inverse correlation between sEGF-R and IL-6 levels. These findings imply a better understanding of EGF-R and IL-6 cross-talk function in melanoma.

Pretreatment serum interleukin-6 concentration as a prognostic factor of overall survival in metastatic malignant melanoma patients treated with biochemotherapy: a retrospective study.

Biological response parameters during biochemotherapy, including chemotherapy with immune modulating agents, have been studied extensively. Of these parameters, interleukin-6 (IL-6) has been implicated in advanced stage disease and tumour recurrence. However, there is limited information available about the significance of IL-6 in metastatic malignant melanoma (MMM). In this study, we evaluated the possible relationship between serum IL-6 level and overall survival. This retrospective study included 125 patients with MMM. Pretreatment serum IL-6 levels were determined using a highly sensitive enzyme-linked immunosorbent assay (ELISA) test. Kaplan-Meier survival curves were constructed and compared using the log-rank test. Cox proportional analysis was performed to assess the predictors of overall survival, which was calculated from the beginning of biochemotherapy until death. In order to establish the possible relationship between IL-6 level and overall survival, patients were divided into two groups according to a cut-off of 5 pg/ml, corresponding to the first quartile obtained by descriptive statistics of the pretreatment IL-6 level in all patients. Thirty-five patients were in the low IL-6 group and 76 patients were in the high IL-6 group. Based on this stratification, overall survival was shown to be affected by IL-6 serum level: it was higher (24.6 months) in the low IL-6 group when compared with the high IL-6 group (9.7 months) (P=0.0006). Furthermore, Cox multivariate analysis including standard melanoma prognostic factors showed that IL-6, as a variable, lactate dehydrogenase (LDH) and tumour burden were significant prognostic factors for overall survival. On the basis of this evidence, the pretreatment serum IL-6 level is a predictive factor of overall survival in MMM.

Surgical margins in cutaneous melanoma (2 cm versus 5 cm for lesions measuring less than 2.1-mm thick).

BACKGROUND: This study addressed the question of whether limited surgery for primary malignant melanoma with a 2-cm margin is as good as a 5-cm margin. An update of a 16-year follow-up is provided. METHODS: Nine European Centers, over a period of 5 years, prospectively randomized 337 patients with melanoma measuring less than 2.1 mm in thickness to undergo a local excision with either a 2-cm or a 5-cm margin. Three hundred twenty-six patients were eligible for statistical analysis. Excluded from the trial were patients older than 70 years; those with melanomas from the toe, nail, or finger; and those with acral-lentiginous melanoma. A separate randomization was performed to independently test an adjuvant treatment with a nonspecific immunostimulant, isoprinosine, compared with observation. The median follow-up time was 192 months (16 years) for the estimation of survival and disease recurrences. RESULTS: There were 22 tumor recurrences in the 2-cm arm and 33 in the 5-cm arm. The median time to disease recurrence was 43 months and 37.6 months, respectively. The 10-year disease-free survival rates were 85% for the group with a 2-cm margin and 83% for the group with a 5-cm margin. There was no difference in the 10-year overall survival rates (87% vs. 86%). Isoprinosine did not demonstrate any activity in this setting. CONCLUSIONS: The authors concluded that for melanoma less than 2.1-mm thick, a margin of excision of 2 cm is sufficient. A larger margin of 5 cm does not appear to have any impact on either the rate or the time to disease recurrence or on survival.

Serum interleukin-6 concentrations as predictive factor of time to progression in metastatic malignant melanoma patients treated by biochemotherapy: a retrospective study.

This retrospective study sought to evaluate the impact of IL-6 concentration on time to progression in advanced melanoma. One hundred and thirty-five patients were included, serum IL-6 levels were determined before (Day 0), at the end of the treatment (Day 49) and at recurrence: the relationship between IL-6 concentration and time to progression (TTP) was also evaluated. The baseline median serum IL-6 level was 16.5 pg/ml. When disease progression was observed, an increase in serum IL-6 level was noted. In order to establish the possible relationship between IL-6 level and TTP, patients were divided into two groups (low and high) using the median IL-6 level (16.5 pg/ml) detected in the pretreatment serum of overall patients as a cut-off. Sixty patients were in the low IL-6 group and 56 patients in the high IL-6 group. Time to progression was calculated from the beginning of treatment to recurrence, and analyzed using the Kaplan-Meier method. Patients with low IL-6 serum concentration showed a significantly (p<0.00001) higher median TTP than patients with high IL-6 level. Patients maintaining a low IL-6 level during the treatment showed the longest median TTP compared with those supporting high levels (24.4 versus 5.5 months). Taken together, our results showed that serum IL-6 level could be considered a predictive marker of recurrent disease in metastatic malignant melanoma.