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

Abstract

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.

Intraocular biopsy of uveal melanoma Risk assessment and identification of genetic prognostic markers

“…We confirmed our findings in a collaborative multicentre study (Dogrusöz et al. ) and constructed a nomogram to demonstrate how the prognostic factors adhere to a total score, which can accurately estimate survival (Fig. ).…”

“…To validate our findings, we conducted a collaborative project with the Leiden group in 2016, merging our cohort of 247 Danish patients with 275 patients treated for uveal melanoma in Leiden (Dogrusöz et al. ). In addition, we created a nomogram based on the effect estimates from the Cox regression so that predictions for survival at different time‐points could be evaluated manually as described by Harrell (Harrell ) (Fig.…”

Prognostic value of chromosomal imbalances, gene mutations, and BAP1 expression in uveal melanoma

“…Monosomy 3 together with 8q gain was found associated with metastatic disease, as already reported . In our series, also monosomy 3 without 8q gain ( n = 9) was associated with metastases, in contrast with previous data derived from larger cohorts . In addition to MLPA, MSA was used to identify cases with isodisomy 3, which carries the same prognostic significance as monosomy 3 but is not detected by MLPA, as well as by all the techniques that measure the number of chromosomes, ie, FISH and CGH .…”

Genetic prognostication in uveal melanoma

“…; Dogrusöz et al. ). Isochromosome 8q leads to gain of material because it results in three copies of 8q while there is only one copy of 8p.…”