Monosomy of Chromosome 3 and an Inflammatory Phenotype Occur Together in Uveal Melanoma

Maat, Willem; Ly, Long V.; Jordanova, Ekaterina S.; Wolff-Rouendaal, D. De; Schalij‐Delfos, Nicoline E.; Jager, Martine J.

doi:10.1167/iovs.07-0786

Cited by 130 publications

(129 citation statements)

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“…In uveal melanoma, however, an inflammatory phenotype is associated with a poor outcome and has been found to be associated with loss of one chromosome 3. 18 Uveal melanoma may show increased numbers of CD3 þ T lymphocytes and CD11b þ macrophages. 19 High densities of inflammatory cells occur more frequently in epithelioid-cell-type tumours, which are especially the tumours with chromosome 3 loss.…”

Section: Prognostic Impact Of Intratumoral Immune Infiltratesmentioning

confidence: 99%

“…19 High densities of inflammatory cells occur more frequently in epithelioid-cell-type tumours, which are especially the tumours with chromosome 3 loss. 18 To understand the cause of the influx of inflammatory cells, one has to study the composition and function of the immune infiltrate, in the context of microenvironmental factors, such as hypoxia. 20 …”

Section: Prognostic Impact Of Intratumoral Immune Infiltratesmentioning

confidence: 99%

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Inflammation in uveal melanoma

Bronkhorst

Jager

2012

Eye

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Leukocytic infiltration is a common feature of human cancers, including those that develop in immunoprivileged sites, such as the eye. The infiltration of myeloid and T cells into tumours is part of the host response against cancer. In uveal melanoma, high densities of immune cells seem to be involved in tumour progression, as they are associated with the loss of one chromosome 3. The nature of this tumour microenvironment might offer therapeutic opportunities.

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Section: Prognostic Impact Of Intratumoral Immune Infiltratesmentioning

confidence: 99%

Section: Prognostic Impact Of Intratumoral Immune Infiltratesmentioning

confidence: 99%

Inflammation in uveal melanoma

Bronkhorst

Jager

2012

Eye

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“…1 Several histologic prognostic factors have been described for this type of cancer, such as large tumor size, involvement of the ciliary body, extrascleral extension, and an inflammatory phenotype. 2,3 Specific genetic alterations that are significantly associated with the development of metastases have been identified, such as monosomy 3. In spite of the development of very precise techniques for detecting chromosomal alterations, such as spectral karyotyping, fluorescence in situ hybridization (FISH), comparative genomic hybridization, and multiplex ligation-dependent probe amplification (MLPA), loss of a complete chromosome (monosomy 3) is still the most important genetic aberration to predict survival, superior to clinical and pathologic features.…”

mentioning

confidence: 99%

Effect of Heterogeneous Distribution of Monosomy 3 on Prognosis in Uveal Melanoma

Bronkhorst

Maat²,

Jordanova³

et al. 2011

Archives of Pathology &Amp; Laboratory Medicine

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in situ hybridization (FISH) analyses on tumor sections and on isolated nuclei showed that even low numbers of cells with monosomy of chromosome 3 adversely affected survival.Objective.-To determine what percentage of uveal melanoma cells with monosomy of chromosome 3 influences patient mortality.Design.-To determine the presence of monosomy 3, karyotyping and FISH on cultured cells and FISH on isolated nuclei were performed on 50 primary uveal melanomas. Clinical and pathologic prognostic factors were assessed and compared with 5-year survival data. Analyses were performed using Cox proportional hazards test, log-rank analysis, sensitivity, specificity, and positive and negative likelihood ratios.Results.-Combined karyotyping and FISH on cultured cells showed monosomy 3 in 19 of 50 cases (38%), whereas determination of the monosomy 3 status by FISH on isolated nuclei with a threshold of 5% assigned 31 of 50 cases (62%) to the monosomy-3 category. When monosomy 3 on isolated nuclei with a cutoff value of 5% was used, a significant difference in 5-year survival was present (hazard ratio, 15.5; P = .007), indicating that monosomy 3 in greater than 5% of tumor cells is related to death due to metastases.Conclusion.-In uveal melanoma, the presence of greater than 5% of cells with monosomy 3, as determined by FISH on isolated nuclei, is associated with the development of metastases within 5 years after enucleation.

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“…Both monosomy 3 analysis using the microsatellite DNA assay and transcriptome profiling have been successfully performed in fine-needle biopsy uveal melanoma specimens taken prior to radiotherapy, and CISH has been shown to work successfully on fine-needle biopsies from breast and lung cancer patients. [28][29][30][31] Previous studies 16,17,23 have shown epithelioid cells to correlate with loss of 1 copy of chromosome 3. In our study, monosomy 3 was detected in 38% of the epithelioid/mixed cell types (Table 5).…”

Section: Commentmentioning

confidence: 99%

“…[15][16][17][18] The dual aim of this study is to adapt the CISH technique to tumor imprints and to lower turnaround time and the costs involved for determining chromosome 3 status in uveal melanoma. Concordance of CISH with 2 current established techniques, FISH and single-nucleotide polymorphism (SNP) array, is evaluated and this method of tumor sampling for the determination of chromosome 3 alterations in uveal melanoma is also discussed.…”

mentioning

confidence: 99%

Evaluation of Chromogenic In Situ Hybridization for the Determination of Monosomy 3 in Uveal Melanoma

Gleeson

Larkin

Horgan

et al. 2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Loss of 1 copy of chromosome 3 is considered a significant indicator of metastatic dissemination in uveal melanoma. Fresh or paraffin-embedded tumor tissue is most commonly used for current cytogenetic techniques for determining chromosome 3 status in uveal melanoma and often requires referral to an external specialist laboratory for analysis.Objectives.-To assess the chromogenic in situ hybridization assay for detecting chromosome 3 alterations using frozen tumor imprints and to compare the results obtained with those obtained by standard fluorescence in situ hybridization or single-nucleotide polymorphism array techniques.Design.-Chromogenic in situ hybridization was performed on 52 frozen uveal melanoma tumor imprints. The genetic status of 26 of the 52 cases had been determined previously by fluorescence in situ hybridization (group 1); the status of 26 cases had been determined using singlenucleotide polymorphism array (group 2).Results.-Chromogenic in situ hybridization was successfully performed on 48 of 52 tumor imprints. Chromogenic in situ hybridization showed excellent agreement in all 24 cases determined by fluorescence in situ hybridization (100% concordance; j ¼ 1; P , .001; 95% confidence interval, 100%-100%), and disagreed in 4 of the 24 cases previously studied by single-nucleotide polymorphism array (83% concordance; j ¼ 0.67; P , .001; 95% confidence interval, 95%-39%). All 4 discordant cases were classified as disomic for chromosome 3 by chromogenic in situ hybridization and monosomic by SNP array. On histologic examination, the 4 discordant cases corresponded to 2 mixed cell tumors and 2 spindle cell tumors.Conclusions.-Chromogenic in situ hybridization using tumor imprints is a reliable technique for determining chromosome 3 status in uveal melanoma. Furthermore, it can also be easily integrated into a routine histopathology laboratory.

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Monosomy of Chromosome 3 and an Inflammatory Phenotype Occur Together in Uveal Melanoma

Cited by 130 publications

References 28 publications

Inflammation in uveal melanoma

Inflammation in uveal melanoma

Effect of Heterogeneous Distribution of Monosomy 3 on Prognosis in Uveal Melanoma

Evaluation of Chromogenic In Situ Hybridization for the Determination of Monosomy 3 in Uveal Melanoma

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