Background. Cutaneous malignant melanoma (CMM) is a heterogeneous disease, acknowledged for its lack of predictability regarding clinical evolution. In order to appreciate a patient’s individual prognosis, an attempt is made to find new tumor markers that parallel the disease progression. Objective. To identify if melanoma inhibitory activity (MIA) protein could represent a tool for selecting high risk early stages melanoma patients. Method. Between 2008 and 2013, 155 patients with CMM were treated in our clinic. 84 of them were classified into stages I and II, according to TNM 2009. MIA serum concentration was measured in all patients and 50 healthy donors. A cut-off value of 9.4？ng/ml was established using the ROC curve. Results. All patients were followed up by periodic investigations every 6 months. We have noticed that 66% of patients with MIA serum values at diagnosis greater than 9.4？ng/mL have relapsed, while only 5% of patients with MIA serum concentration below the estimated threshold, recurred during the follow-up period . The death risk was 12 times higher in pathological MIA group of patients . Conclusions. Our data suggest that MIA is an independent prognostic factor for patients with localized CMM. 1. Introduction Malignant melanoma represents the cutaneous neoplasia with the highest metastatic potential and a relatively unpredictable evolution, even in early stages. Fortunately, however, the detection of the disease in a localized phase allows it to be cured in most cases [1]. Statistics show that about 30% of people diagnosed with cutaneous malignant melanoma (CMM) develop metastases [2]. In these circumstances, finding new tools to identify those patients who although classified in stage I or II, so theoretically with a favorable outcome, still have a high risk of dissemination, represents a priority. A possibility in this regard might be the discovery of tumor markers whose expression in the blood stream would mirror the disease development. Dozens of substances have been described which were deemed to have prognostic capacity in different stages of CMM. This presumed prognostic ability was suggested by the parallelism between serum concentration of these markers and body tumor burden that was noted in a significant percentage of cases. Nevertheless, only two of them are widely accepted: serum lactate dehydrogenase (LDH) and protein S100 [3, 4]. In recent years, researches in the field of autocrine growth-regulatory factors have led to the discovery of a new serum tumor marker, melanoma inhibitory activity (MIA), a protein synthesized
References
[1]
S. Liu, P. Kirschmeier, J. Simon, C. Seidel-Dugan, and M. Puhlmann, “Prognostic and predictive molecular markers in cutaneous malignant melanoma: the first step toward personalized medicine,” Current Pharmacogenomics and Personalized Medicine, vol. 6, no. 4, pp. 272–294, 2008.
[2]
R. Essner, J. H. Lee, L. A. Wanek et al., “Contemporary surgical treatment of advanced-stage melanoma,” Archives of Surgery, vol. 139, no. 9, pp. 961–967, 2004.
[3]
C. M. Balch, J. E. Gershenwald, S. Soong et al., “Final version of 2009 AJCC melanoma staging and classification,” Journal of Clinical Oncology, vol. 27, no. 36, pp. 6199–6206, 2009.
[4]
S. Mocellin, G. Zavagno, and D. Nitti, “The prognostic value of serum S100B in patients with cutaneous melanoma: a meta-analysis,” International Journal of Cancer, vol. 123, no. 10, pp. 2370–2376, 2008.
[5]
A. Bosserhoff, “Melanoma inhibitory activity (MIA): an important molecule in melanoma development and progression,” Pigment Cell Research, vol. 18, no. 6, pp. 411–416, 2005.
[6]
A. K. Bosserhoff, “Mia1,” UCSD-Nature Molecule, 2006.
[7]
A.-K. Bosserhoff, R. Stoll, J. P. Sleeman, F. Bataille, R. Buettner, and T. A. Holak, “Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity,” Laboratory Investigation, vol. 83, no. 11, pp. 1583–1594, 2003.
[8]
S. Kruijff and H. J. Hoekstra, “The current status of S-100B as a biomarker in melanoma,” European Journal of Surgical Oncology, vol. 38, no. 4, pp. 281–285, 2012.
[9]
M. Al-Shaer, D. Gollapudi, and C. Papageorgio, “Melanoma biomarkers: vox clamantis in deserto (review),” Oncology Letters, vol. 1, no. 3, pp. 399–405, 2010.
[10]
A.-K. Bosserhoff, M. Kaufmann, B. Kaluza et al., “Melanoma-inhibiting activity, a novel serum marker for progression of malignant melanoma,” Cancer Research, vol. 57, no. 15, pp. 3149–3153, 1997.
[11]
R. Meral, D. Duranyildiz, F. Tas et al., “Prognostic significance of melanoma inhibiting activity levels in malignant melanoma,” Melanoma Research, vol. 11, no. 6, pp. 627–632, 2001.
[12]
M. A. Hofmann, F. Gussmann, A. Fritsche et al., “Diagnostic value of melanoma inhibitory activity serum marker in the follow-up of patients with stage I or II cutaneous melanoma,” Melanoma Research, vol. 19, no. 1, pp. 17–23, 2009.
[13]
M. Essler, A. Link, B. Belloni et al., “Prognostic value of [18F]-fluoro-deoxy-glucose PET/CT, S100 or MIA for assessment of cancer-associated mortality in patients with high risk melanoma,” PLoS ONE, vol. 6, no. 9, Article ID e24632, 2011.
[14]
M. A. Hofmann, B. Schicke, A. Fritsch et al., “Impact of lymph node metastases on serum level of melanoma inhibitory activity in stage III melanoma patients,” Journal of Dermatology, vol. 38, no. 9, pp. 880–886, 2011.
[15]
J. M. Auge, R. Molina, X. Filella et al., “S-100β and MIA in advanced melanoma in relation to prognostic factors,” Anticancer Research, vol. 25, no. 3, pp. 1779–1782, 2005.
