Prognostic Implications of Tumor Diameter in Association With Gene Expression Profile for Uveal Melanoma

Walter, Scott D.; Chao, Daniel L.; Feuer, William J.; Schiffman, Joyce C.; Char, Devron H.; Harbour, J. William

doi:10.1001/jamaophthalmol.2016.0913

Cited by 108 publications

(98 citation statements)

References 18 publications

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“…RNA and its inherent instability compared to DNA may be more prone to handling error, and perhaps this may be the source of an inherently inaccurate test in the setting of GEP. It has also been suggested that the size of the tumor must be considered when interpreting a Class 1 or a Class 2 test result [21]. However, we found that the average tumor size was not statistically different between concordant and discordant groups of patients in our series.…”

Section: Discussioncontrasting

confidence: 74%

Comparison of Gene Expression Profiling and Chromosome 3 Analysis by Fluorescent in situ Hybridization and Multiplex Ligation Probe Amplification in Fine-Needle Aspiration Biopsy Specimens of Uveal Melanoma

et al. 2017

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Purpose: The aim of this paper was to assess the concordance between results of DecisionDx-UM specific gene expression profiling (GEP) and fluorescence in situ hybridization (FISH) for chromosome 3 analysis, and between DecisionDx-UM GEP and multiplex ligation probe amplification (MLPA) in uveal melanoma undergoing intraoperative fine-needle aspiration biopsy (FNAB) for metastatic prognostication during brachytherapy. Methods: We retrospectively reviewed consecutive patients diagnosed with posterior uveal melanoma who underwent intraoperative FNAB prior to placement of an iodine-125 radioactive plaque between 2012 and 2014. Two cohorts of patients were identified: Cohort 1 - tumors in which both GEP and FISH results were obtained, and Cohort 2 - tumors in which both GEP and MLPA results were obtained. Results: Forty-four patients were identified for Cohort 1. FISH and GEP results were discordant in 7 tumors (15.9%). Forty-three patients were identified for Cohort 2. MLPA and GEP were discordant in 7 tumors (16.3%). Conclusions: Discordance between GEP and chromosome 3 status by FISH and MLPA occurred in our series at a rate of 15.9 and 16.3%, respectively. Caution must be advised when counseling a patient with a good-prognosis GEP “Class 1” result that the uveal tumor may actually harbor monosomy 3, which is associated with a poor prognosis for metastasis in nearly 20% of the patients.

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Section: Discussioncontrasting

confidence: 74%

Comparison of Gene Expression Profiling and Chromosome 3 Analysis by Fluorescent in situ Hybridization and Multiplex Ligation Probe Amplification in Fine-Needle Aspiration Biopsy Specimens of Uveal Melanoma

et al. 2017

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“…26,27 Other authors have since also addressed the question as to whether the combined use of the TNM/AJCC staging system and genomic characteristics of the tumor will allow for better risk stratification. 28,29 As proposed earlier, 8,26,27 integrating the TNM/AJCC staging system with genetics may enhance prognostication in UM. This is supported by the findings of a recent study by Bagger et al 30 in a Danish cohort of 153 patients, which indicated that AJCC stage III and aberrations in chromosome 3 and 8 are independent prognostic factors.…”

mentioning

confidence: 95%

The Prognostic Value of AJCC Staging in Uveal Melanoma Is Enhanced by Adding Chromosome 3 and 8q Status

Doğrusöz

Bagger

Duinen

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Dogrusöz M, Bagger M, van Duinen SG, et al. The prognostic value of AJCC staging in uveal melanoma is enhanced by adding chromosome 3 and 8q status. Invest Ophthalmol Vis Sci. 2017;58:833-842. DOI:10.1167/ iovs.16-20212 PURPOSE. The American Joint Committee on Cancer (AJCC) staging system has been validated for use as a prognostic parameter in uveal melanoma (UM). We studied whether adding information regarding chromosome 3 and 8q status further enhances the prognostic value of this staging system. METHODS.We retrospectively studied a cohort of 522 patients who had been treated for UM in two different centers between 1999 and 2015. The mean follow-up time was 47.7 months. Cumulative incidence curves were generated and regression analyses were performed for different combinations of AJCC staging and chromosome status. Death due to UM metastases was the primary endpoint.RESULTS. In AJCC stage I cases, only patients with monosomy 3 as well as chromosome 8q gain died due to UM metastases (P < 0.001). Among patients with stage II and III tumors, those with monosomy 3 plus gain of chromosome 8q had the worst prognosis, whereas the clinical outcome of those with only one of these aberrations was intermediate (P < 0.001). Patients without monosomy 3 and 8q gain showed favorable prognosis, independent of their tumor's AJCC stage. In cases with monosomy 3, 8q gain, or both, adding AJCC stage improved the predictive value. Multivariable regression analyses demonstrated that AJCC staging and chromosome 3 and 8q status contain independent information about survival status.CONCLUSIONS. Combining information on AJCC staging and chromosome 3 and 8q status allows a more accurate prognostication in UM. We conclude that the prognostic value of the AJCC staging system can be improved by adding information regarding chromosome 3 and 8q status.

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“…As a greater proportion of smaller tumors are being treated, recent research has demonstrated that in addition to a class 2 gene expression profile, LBD is also an independent statistically significant predictor of survival [18,19]. This suggests that metastasis is not only a product of a tumor's RNA activity, but also a result of tumor size [18,19,27].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling as an Adjunctive Measure to Guide the Management of Indeterminate, High-Risk Choroidal Melanocytic Lesions: A Pilot Study

et al. 2018

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Purpose: To describe our early experience with gene expression profiling (GEP) assessment for juxtafoveal, subfoveal, and peripapillary indeterminate high-risk melanocytic lesions to assist in making early treatment decisions in patients who did not feel comfortable with either close observation or definitive treatment. Methods: A prospective cohort of patients with indeterminate lesions who underwent GEP were enrolled. Nonparametric statistical analysis was utilized given the small sample size. Results: Fifteen patients were included in this series. Six (40%) were class 1A and 9 (60%) class 1B. Class 1A and 1B lesions had a median of three and four clinical risk factors, respectively (p = 0.27). There was no statistically significant difference for the largest basal diameter between the classes (p = 0.31); however, class 1B lesions were thicker than class 1A lesions (p = 0.03). None of the class 1A lesions showed definite growth or metastasis over a mean follow-up period of 17.1 ± 1.8 months from fine needle aspiration biopsy. All class 1B patients opted for plaque brachytherapy, and to date none of these patients have developed metastasis, with a mean follow-up of 18.7 ± 8.4 months. Conclusion: There may be a role for GEP assessment in high-risk, indeterminate, posteriorly located choroidal lesions to assist in treatment planning.

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Prognostic Implications of Tumor Diameter in Association With Gene Expression Profile for Uveal Melanoma

Cited by 108 publications

References 18 publications

Comparison of Gene Expression Profiling and Chromosome 3 Analysis by Fluorescent in situ Hybridization and Multiplex Ligation Probe Amplification in Fine-Needle Aspiration Biopsy Specimens of Uveal Melanoma

Comparison of Gene Expression Profiling and Chromosome 3 Analysis by Fluorescent in situ Hybridization and Multiplex Ligation Probe Amplification in Fine-Needle Aspiration Biopsy Specimens of Uveal Melanoma

The Prognostic Value of AJCC Staging in Uveal Melanoma Is Enhanced by Adding Chromosome 3 and 8q Status

Gene Expression Profiling as an Adjunctive Measure to Guide the Management of Indeterminate, High-Risk Choroidal Melanocytic Lesions: A Pilot Study

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