Angela Sandru

Prognostic Value of Melanoma Inhibitory Activity Protein in Localized Cutaneous Malignant Melanoma

Background. Cutaneous malignant melanoma (CMM) is a heterogeneous disease, acknowledged for its lack of predictability regarding clinical evolution. In order to appreciate a patients 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 (P = 0.000). The death risk was 12 times higher in pathological MIA group of patients (P = 0.0001). Conclusions. Our data suggest that MIA is an independent prognostic factor for patients with localized CMM.

Clinical value of Melanoma Inhibitory Activity in stratifying malignant melanoma patients

Background Malignant melanoma (MM) is a heterogeneous disease, well-known for its unpredictable clinical course and lack of response to most systemic therapies. Furthermore in some parts of the world it has quite an epidemic nature, with an incidence that has increased steadily in the last 30 years [1]. Therefore the characterization of new tumor markers that could better suggest the patient outcome has become a priority for many research centers. Melanoma Inhibitory Activity (MIA) is a protein highly expressed and secreted by malignant melanocytes [1,2], without being identified in benign melanocytes or other normal skin cells [3]. More, the induction of MIA synthesis seems to be an early event in carcinogenesis, taking into account that all in situ tumors express it. The objective of this study was to assess the significance of increased serum MIA concentration in MM patients with no metastases at primary diagnoses. Materials and methods Between 2008-2012 we have collected 200 blood samples from 150 patients with non-metastatic MM and 50 healthy donors. The patients were staged according to TNM classification 2009 as follows: 28 in stage I, 72 in stage II and 50 in stage III. The blood was withdrawn after the primary tumor excision and before any other treatment. MIA was measured by a high sensitivity ELISA method, with a kit produced by Roche Diagnostics. Using the ROC curve, MIA cut-off value was set at 9.4 ng/ml [4]. Results We estimated overall survival (OS) and disease free survival (DFS) for the entire lot and for each stage separately, according to MIA cut-off level. The length of follow-up was 44 month, from the moment of MIA measurement. Univariate Cox regression suggested that patients with an increased MIA serum concentration had a three times higher risk of relapse (HR=3.3895) and death (HR = 2.7597) than patients with values under the calculated threshold (p=0.000). More important is that MIA keeps statistical significance in multivariate analyses, predicting risk of death or relapse after corrections for clinical stage. Conclusions In our study, MM patients with a MIA serum concentration above 9.4 ng/ml had a worse DFS (p=0.0109) and OS (p=0.0009) than patients with values below 9.4 ng/ml. We consider that MIA serum concentration is a valuable prognostic factor and could become a tool for selecting patients at risk for developing metastases rendering them eligible for neoadjuvant treatment.

Management of Breast Cancer Locoregional Recurrence

Breast cancer recurrence represents a challenge for clinicians because the management is not standardized and usually requires a multidisciplinary approach. This is the key for a good long term disease control and for a management with curative intent. The local recurrence in breast cancer appears after breast conserving treatment (BCT) or after mastectomy, and the regional recurrence involves the ipsilateral axillary, internal mammary or supraclavicular lymph nodes. Local recurrence prognosis after BCT seems to be better than after mastectomy regarding distant metastases occurrence and overall survival. Prognosis of axillary recurrence is better than prognosis of supraclavicular and internal mammary recurrence. Locoregional recurrence in breast cancer represents rather a marker for the appearance of distant metastases than a determinant factor for them. Management options for locoregional recurrence of cancer require multidisciplinary input decision making and for this reason the multidisciplinary tumor-board (MTD) is very important. Each patient should receive the best individualized oncologic treatment.

Simultaneous determination of two serum tumor markers in assessing malignant melanoma patients

Background The incidence of cutaneous malignant melanoma (MM) continues to raise despite extensive prevention programs. If localized disease can be cured, the prognosis of metastatic melanoma is grim. Therefore, reliable methods to detect patients at risk for disease progression are sought. Field of tumor markers has captured attention because it allows the first steps toward personalized medicine. A positive tumor marker has a limited ability to correctly detect all sick people, so it was proposed to simultaneously measure several markers in order to improve their performance [1,2]. S100 and Melanoma Inhibitory Activity (MIA) are most frequently used for monitoring MM patients. Both proteins have a high specificity and their expression correlates with body tumor burden [3].

Melanoma Inhibitory Activity and regional lymph node status in malignant melanoma patients

Background For many cancers, and malignant melanoma (MM) makes no exception, regional lymph node (RLN) status is decisive for subsequent patients’ outcome. But particularly for MM, stage III comprises a very heterogeneous group of patients, from those with microscopic invasion diagnosed by sentinel node (SN) biopsy to those with matted nodes. Correct staging of patients with clinically free RLN requires SN biopsy. Because this is an invasive maneuver, various substitutes were searched. Thus, in literature there are conflicting references to a possible link between Melanoma Inhibitory Activity (MIA) serum concentration and SN status [1,2]. MIA, a protein secreted by malignant melanocytes into the extracellular space, blocks the melanoma cells attachment to fibronectin and laminin. Thus MIA increases malignant cells mobility and promotes local invasion and metastasis [3]. In this context, we sought a connection between RLN status and MIA serum concentration in our group of patients.