Clinical and histopathological features and immunoreactivity of human choroidal and ciliary melanomas as prognostic factors for metastasis and death

Simões, Camila; Call, Mindy K.; Corrêa, Zélia M.; Spaulding, Abbot G.; Augsburger, James J.

doi:10.1007/s00417-011-1769-7

Cited by 9 publications

(6 citation statements)

References 38 publications

(52 reference statements)

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“…Basic characteristics of the presented pool of patients are comparable with those introduced in other published studies [16]. From among the clinical prognostic factors our results confirmed the negative prognostic value of the tumor size, "T" stage of the TNM classification and the mixed cytomorphological type of the neoplasm [17][18][19][20].…”

Section: Discussionsupporting

confidence: 83%

Prognostic value of apoptosis inducing factor in uveal melanoma

Krásnik¹,

Furdová²,

Svetlosakova³

et al. 2017

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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.

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Section: Discussionsupporting

confidence: 83%

Prognostic value of apoptosis inducing factor in uveal melanoma

Krásnik¹,

Furdová²,

Svetlosakova³

et al. 2017

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“…Kadkol et al [40] reported that the level of SPP1 expression was increased in the serum of patients with UM metastasis, and that tumors with looping high-risk vasculogenic mimicry patterns had increased expression of osteopontin. Another study [41] also looked at protein expression using a monoclonal antibody and did not observe a relation between expression and survival. In contrast to Kadkol and Simoes, we looked at mRNA and observed that decreased levels of SPP1 mRNA were associated with an unfavorable prognosis in UM.…”

Section: Discussionmentioning

confidence: 99%

Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma

Souri

Wierenga

Weeghel

et al. 2019

Cancers

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One of the characteristics of prognostically infaust uveal melanoma (UM) is an inflammatory phenotype, which is characterized by high numbers of infiltrating T cells and macrophages, and a high HLA Class I expression. We wondered how this inflammation is regulated, and considered that one of the most important regulators of inflammation, the NFkB pathway, might play a role. We analyzed 64 UM samples for expression of HLA Class I, its regulators, and of members of the NFkB transcription family, using an Illumina HT12V4 array. HLA Class I expression and infiltrating immune cells were also determined by immunohistochemical staining. Information was obtained regarding chromosome status by Affymetrix Nsp array. Our analysis shows that expression of NFkB1, NFkB2 and RELB positively correlates with the level of HLA Class I expression and the number of infiltrating T cells and macrophages, while SPP1 and PPARγ are negatively correlated. Increased levels of NFkB1 and NFkB2 and decreased levels of SPP1 and PPARγ are seen in Monosomy 3/BAP1-negative tumors. This is also the case in non-inflammatory UM, indicating that our observation not only involves infiltrating leukocytes but the tumor cells themselves. We report that the NFkB pathway is associated with inflammation and HLA Class I expression in UM, and is upregulated when BAP1 expression is lost.

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“…The study of the expression and copy number status of genes such as leucine zipper tumour suppressor 1 ( LZTS1 ), located on the 8p22 chromosomal band, has been considered in the evaluation of the prognosis of UM (Simoes et al. 2011; Wan et al. 2020); Onken et al., (2008a, 2008b) suggested that this gene acts as a metastatic regulator in UM.…”

Section: Introductionmentioning

confidence: 99%

Role of somatic mutations and chromosomal aberrations in the prognosis of uveal melanoma in a Spanish patient cohort

Silva-Rodríguez

Bande

Fernandez-Diaz

et al. 2021

Acta Ophthalmologica

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Background Uveal melanoma (UM) has a high tendency to cause liver metastases. Metastatic disease is fatal, with a low survival rate. There are two large groups of UMs that, according to their risk of metastatic disease, can be divided into risk subgroups based on histopathological, cytogenetic and molecular characteristics. The presence of somatic mutations in certain genes may explain the origin and prognosis of these tumours. Methods Forty‐six UM samples previously classified as high or low metastatic risk according to chromosome 3 copy number status were tested for somatic mutations. A multi‐gene targeting strategy was adopted, and sequencing was performed using AmpliSeq technology. Results Mutations were found in all major UM‐related genes. BAP1 mutations confer an increased risk of metastases in high‐risk tumours; thus, this gene acts as a strong prognostic predictor in UM. The presence of somatic mutations in LZTS1 did not show significant differences in the risk of metastases. Conclusions This result supports the idea that exploring mutations and copy number variations in UM provides insights into patient outcomes. Genetic tests allow the determination of accurate personalized molecular profiles with a fundamental prognostic purpose.

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Clinical and histopathological features and immunoreactivity of human choroidal and ciliary melanomas as prognostic factors for metastasis and death

Abstract: Our study suggests that conventional clinical and histopathological prognostic factors, and immunoexpression of β-catenin and LZTS1 combined may allow better prognostication of metastasis than clinical and histomorphological factors alone.

Cited by 9 publications

References 38 publications

Prognostic value of apoptosis inducing factor in uveal melanoma

Prognostic value of apoptosis inducing factor in uveal melanoma

Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma

Role of somatic mutations and chromosomal aberrations in the prognosis of uveal melanoma in a Spanish patient cohort

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