Prognostic value of apoptosis inducing factor in uveal melanoma.

In malignant tumors including uveal melanoma there is a continuous effort in search for additional and relevant factors with predictive value and possible therapeutic indications. In the present work we evaluated the 5-year mortality in a group of patients with surgically treated uveal melanoma and its relation to selected demographic, clinical and histopathological parameters, including the expression of apoptosis inducing factor (AIF) in the neoplastic tissue.We analyzed retrospectively the clinical data of patients with uveal melanoma treated surgically (enucleation, endoresection, exenteration) in the period from 2001 to 2007 (n=54). Immunohistochemical detection of AIF expression in formalin fixed and in paraffin embedded tissue samples was evaluated semiquantitatively, intensity and percentage multiplicative Quick Score (QS) was calculated and compared between patients with over 5 year (n=32) and less than 5 year (n=22) survival. In the analyzed group of 54 patients the 5 year mortality was 41 %. We confirmed the negative prognostic significance of some of the known prognostic factors as the tumor size and volume, T3 and T4 stage in the TNM classification and the mixed histological type of the tumor. Immunohistochemistry performed on 49 melanoma specimens showed AIF cytoplasmic positivity, no nuclear translocation was detected. The cut-off value of AIF expression QS ≥ 4 (18) in tumor cells separated the 5 year survival of patients (P = 0.018), odds ratio 5.2 (1.24 - 21.73). Moderate and strong expression of AIF in tumor cells also correlated with less favorable prognosis. Confocal microscopy proved colocalization of AIF with mitochondrial marker in neoplastic cells.The prognosis of patients with uveal melanoma can be more accurate with inclusion of immunohistochemical detection of AIF expression. Increased expression of the AIF protein appears as a new negative prognostic factor predicting the 5 year survival.

[Selected prognostic factors of malignant uveal melanoma]. / Vybrané prognostické faktory malígneho melanómu uvey.

Malignant uveal melanoma is the most common intraocular tumor in adults. Despite very good local treatment results, patients' survival has not improved in the last decades. The main cause of death is metastatic spread, which occurs with a variable time delay after tumor discovery in 50% of patients. After metastasis development the mean survival rate decreases to less than 6 months. Progression to metastatic disease is associated with different prognostic factors. The spectrum of conventional clinical and histopathologic prognostic factors like age, tumor size, location, extrascleral growth, histopathologic cell type, vascularisation, invasion of sclera, etc., has been enlarged by using new immunological, molecular, immunohistochemical and cytogenetical methods. Current research also focuses on development of an adjuvant systemic therapy which could delay or prevent metastasis development in high-risk patients. It is necessary to determine reliable prognostic factors in order to select potential candidates for such a systemic treatment. In this article we present a short overview of known prognostic factors of uveal melanoma.