Frequency and implications of discordant gene expression profile class in posterior uveal melanomas sampled by fine needle aspiration biopsy

Am J Ophthalmol. 2015 Feb;159(2):248-56. doi: 10.1016/j.ajo.2014.10.026. Epub 2014 Nov 5.


Purpose: To determine the frequency of discordant gene expression profile (GEP) classification of posterior uveal melanomas sampled at 2 tumor sites by fine-needle aspiration biopsy (FNAB).

Design: Prospective single-institution longitudinal study performed in conjunction with a multicenter validation study of the prognostic value of GEP class of posterior uveal melanoma cells for metastasis and metastatic death.

Methods: FNAB aspirates of 80 clinically diagnosed primary choroidal and ciliochoroidal melanomas were obtained from 2 tumor sites prior to or at the time of initial ocular tumor treatment and submitted for independent GEP testing and classification. Frequency of discordant GEP classification of these specimens was determined.

Results: Using the support vector machine learning algorithm favored by the developer of the GEP test employed in this study, 9 of the 80 cases (11.3% [95% confidence interval: 9.0%-13.6%]) were clearly discordant. If cases with a failed classification at 1 site or a low confidence class assignment by the support vector machine algorithm at 1 or both sites are also regarded as discordant, then this frequency rises to 13 of the 80 cases (16.3% [95% confidence interval: 13.0%-19.6%]).

Conclusion: Sampling of a clinically diagnosed posterior uveal melanoma at a single site for prognostic GEP testing is associated with a substantial probability of misclassification. Two-site sampling of such tumors with independent GEP testing of each specimen may be advisable to lessen the probability of underestimating an individual patient's prognostic risk of metastasis and metastatic death.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Biopsy, Fine-Needle
  • Brachytherapy
  • Choroid Neoplasms / classification*
  • Choroid Neoplasms / genetics
  • Choroid Neoplasms / mortality
  • Choroid Neoplasms / pathology
  • Female
  • Gene Expression Profiling / classification*
  • Gene Frequency*
  • Humans
  • Male
  • Melanoma / classification*
  • Melanoma / genetics
  • Melanoma / mortality
  • Melanoma / secondary
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Polymerase Chain Reaction
  • Prognosis
  • Prospective Studies
  • Transcriptome


  • Neoplasm Proteins