Melanoma tumors are highly heterogeneous, comprising of different cell types that vary in their potential for growth and invasion.,Heterogeneous expression of the Microphthalmia-associated Transcription Factor (MITF) and the POU domain transcription factor BRN2 (POU3F2) has been found in malignant melanoma.,Changing expression of these transcription factors as the disease progresses has been linked to the metastatic mechanism of phenotype switching.,We therefore investigated the effects of MITF and BRN2 expression in melanoma growth and metastasis.,Depletion of MITF resulted in a cell population that had a slowed cell cycle progression, was less invasive in vitro and had hindered tumor and metastasis forming ability in mouse xenograft studies.,BRN2 depletion left a cell population with intact proliferation and invasion in vitro; however metastatic growth was significantly reduced in the mouse xenograft model.,These results suggest that the proliferative population within melanoma tumors express MITF, and both MITF and BRN2 are important for metastatic growth in vivo.,This finding highlights the importance of BRN2 and MITF expression in development of melanoma metastasis.
Rationale: Malignant melanoma (MM) is the cutaneous neoplasia with the greatest mortality rates and one of the malignancies with the highest potential of dissemination.,The prognosis of patients with metastatic MM is grim, with a 5-years survival rate between 5-19%, and is dictated by the location and the number of metastases.,Objective: We aimed to estimate the survival of patients with metastatic MM from our study and find out if the metastasis’ location influences survival.,Methods and results: Between 2008 and 2013, 155 patients with cutaneous MM were diagnosed in our clinic.,All the patients were staged according to 2009 AJCC staging system.,The median follow-up period was of 24 months.,Survival was calculated by using the Kaplan-Meier method with a confidence level of 95%.,40.5% of the patients developed metastases in different organs, especially the brain.,80.6% of those with metastases died during the study.,The median overall survival, estimated for the entire group of patients who developed metastases, was of 5.3 months.,Discussion: The influence of metastases distribution on the overall survival was examined and it was noticed that there were statistically significant differences between the risks of death of various groups of patients, depending on metastasis topography.,Thus, the death probability of a patient with brain metastases is twice that of a patient with digestive metastasis, about 7 times higher than that of a patient with lung metastasis (p = 0.0004) and 12 times higher than the death risk of a patient with extra-regional lymph nodes or subcutaneous metastasis (p = 0.0000).