ATRX Loss in the Development and Prognosis of Conjunctival Melanoma.

Metastatic disease is linked to promoter mutations in conjunctival melanomas (CM). Both promoter and mutations are associated with faulty telomere maintenance. This study aimed to determine the prognostic value of ATRX loss in conjunctival melanocytic lesions. Eighty-six conjunctival melanocytic lesions from the Rotterdam Ocular Melanoma Study group were collected. status and promoter status were determined using immunohistochemical staining and molecular diagnostics, respectively. None of the nevi ( = 16) and primary acquired melanosis (PAM) without atypia ( = 6) showed ATRX loss. ATRX loss was found in 2/5 PAM with atypia without CM and in 8/59 CM. No cases with a promoter mutation ( = 26) showed ATRX loss. Eight/eleven metastatic CM harbored a promoter mutation, two other metastatic CM showed ATRX loss and one metastatic case showed no promoter/ alterations. In conclusion ATRX loss and promoter mutations are only found in (pre)malignant conjunctival melanocytic lesions, with most metastatic cases harboring one of these alterations, suggesting that both alterations are associated with adverse behavior. Similar to promoter mutations, ATRX loss may be used as a diagnostic tool in determining whether a conjunctival melanocytic lesion is prone to having an adverse course.