Abstract
Low-grade appendiceal mucinous neoplasms (LAMNs) can occur concurrently with appendiceal sessile serrated lesions (SSLs). To interrogate relatedness, we performed multigene and immunohistochemical characterizations of paired and unpaired SSLs and LAMNs. We evaluated 62 serrated lesions from 50 appendectomy specimens for hotspot mutations in BRAF, KRAS, and GNAS genes. Cases were subdivided into 3 groups: 20 unpaired SSLs, 18 unpaired LAMNs, and 12 with an SSL and concurrent LAMN. β-catenin and Annexin A10 immunostaining were performed on the SSL and LAMN components in the 12 paired cases, and 14 colonic SSLs served as controls. There was no significant difference in KRAS hotspot mutation rates in appendiceal SSLs (17/26; 65.4%) and LAMNs (16/30; 53.3%) (p=0.42). BRAF V600E was identified in a single case (1/50; 2.0%) of SSL and concurrent LAMN (p=1.0). Mutations in GNAS were more common in LAMNs (6/30; 20.0%) than in SSLs (1/31; 3.2%) (p=0.05). The molecular genotypes between paired SSLs and LAMNs were concordant in most cases (10/12; 83.3%). Annexin A10 immunostaining was significantly greater in colonic SSLs (14/14; 100%) than in appendiceal SSLs (1/12; 8.3%) (p<0.0001). β-catenin immunostaining was significantly increased in LAMNs (10/12; 83.3%) compared with their paired appendiceal SSLs (2/12; 16.7%) (p=0.003). Overall, appendiceal SSLs are predominantly driven by KRAS mutations and are not characterized by Annexin A10 immunostaining. Our data suggestthat at least a subset of LAMNs may arise from a precursor SSL in which GNAS mutations and/or upregulation of the WNT signaling pathway are likely key events modulating this progression.
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