SAT-068 A Precise Prevalence Of Genotypes And Histological Subtypes Of Consecutive JapanesePA CasesUndergoing Surgery From 2012 To 2017

Abstract

Recent advances of molecular analysis and the development of specific monoclonal antibody against aldosterone synthase (CYP11B2) have indeed established the histological subtypes based on the localization of aldosterone overexcess and revealed the association between genotype and clinicopathological phenotype. In particular, several kinds of aldosterone-driver gene somatic mutation have been reported, including KCNJ5, ATP1A1, ATP2B3, CACNA1D and CTNNB1. Among them, KCNJ5 somatic mutation was most frequently detected in aldosterone-producing adenoma although the prevalence of PA genotypes was markedly different among ethnic groups. The precise prevalence of genotype and histological subtypes in Japanese PA patients in large cohort has virtually remained unknown. Therefore, in this study, consecutive 125 unilateral PA cases entirely composed of Japanese patients who underwent surgery from 2012 to 2017 were histologically and genetically evaluated in order to clarify the precise prevalence of genotypes and histological subtypes among Japanese PA patients. 125 cases were precisely classified as follows based on detailed histopathological examination; single APA (84.0%), multiple (more than two) APAs (1.6%), APA + NFA (non-functional adenoma) (5.6%), MN (multiple adrenocortical micronodules) (5.6%), MN+NFA (2.4%) and DH (diffuse hyperplasia of the zona glomerulosa) (0.8%). Adrenal glands harboring single APA were further examined for genotyping. Among them, 67% harbored KCNJ5 mutated (G151R: 39.6%, L168R: 26.4%, T158A: 1.1%) and 33% harbored wild type. 5.4% of single APA clinically combined with Subclinical Cushing's syndrome, all harbored KCNJ5 mutated APAs. The results of our large-scaled analysis did firstly reveal the precise prevalence of histological subtypes and genotypes among Japanese PA patients who underwent surgery. Approximately 10% of unilateral resected PA cases histologically harbored non-neoplastic subtypes such as MN and DH. In addition to those non-neoplatic subtypes, 15% of unilateral resected PA cases other than single APA definitely required CYP11B2 immunohistochemistry in order to precisely detect the responsible lesions for aldosterone overexcess, distinguishing from the non-functional adrenocortical lesions or/and detecting more than two responsible lesions.