P3632 - Colon Carcinomas Shown to Arise From Sessile Serrated Lesions (SSLs) at Pathology Show Frequent Dysplasia and Features of the Serrated Neoplasia Pathway

Anupama Gupta, MBBS¹, Rondell Graham, MBBS, MD¹, Bahar Saberzadeh-Ardestani, MBBS², Seth Sweetser, MD¹, Frank A. Sinicrope, MD^1
1Mayo Clinic, Rochester, MN; ²Yale school of Medicine, New Haven, CT

Introduction: Serrated sessile lesions (SSLs) are presumed precursors of colorectal cancer (CRC) yet are rarely identified in direct association with the cancer histopathologically, in contrast to adenomas. SSLs are believed to arise from the serrated neoplasia pathway that is characterized by BRAF mutation, a methylator phenotype, and frequent deficient mismatch repair (d-MMR). To provide further evidence of the role of SSLs as precursor lesions of CRC, we sought to identify SSLs in direct association with CRCs at surgical pathology and examined their BRAF and MMR status. Whereas BRAF^V600E has not been shown to be prognostic in d-MMR tumors, BRAF^V600E is adversely prognostic in pMMR CRCs.

Methods: We retrospectively reviewed a surgical pathology database at Mayo Clinic (2006 -2017) to identify colon carcinomas (CCs) arising within or contiguous to an SSL. From the electronic health record, we reviewed surgical pathology and colonoscopy reports and abstracted demographic and tumor clinicopathological data. Immunohistochemical status of mismatch repair (MMR) proteins and BRAF (V600E) status, where available, were determined and recorded.

Results: Colon adenocarcinomas (N=42) arising within or contiguous to an SSL were identified. Median patient age was 75 years, 32 (76.2%) were female and 39 (92.8%) were located in the proximal colon. Epithelial dysplasia was identified in 18 (43%) CC-associated SSLs. TNM stage of SSL-associated CC included one stage 0 (2.5%), 14 stage I (35%), 12 stage II (30%), 11 stage III (27.5%), and 2 stage IV (5%) tumors. Of the 42 cancers, 33 (78.6%) had dMMR and 9 (21.4%) showed proficient MMR (pMMR). Of 37 cancers with available BRAF data, 32 (86.5%) tumors with dMMR harbored BRAF^V600E and 5 ( 13.5%) pMMR tumors had the V600E mutation. Among the 33 dMMR cases, 30 (85.7%) show loss of MLH1; 3 were not tested.

Discussion: We observed SSLs with frequent dysplasia in direct association with CCs. A majority of SSL-associated cancers were proximal, harbored BRAFV600E and showed sporadic dMMR due to loss of MLH1. SSL-associated cancers also include pMMR tumors with BRAF^V600E indicating that both can develop through the serrated neoplasia pathway with reported distinct differences in treatment response and prognosis.


Disclosures:


Anupama Gupta, MBBS¹, Rondell Graham, MBBS, MD¹, Bahar Saberzadeh-Ardestani, MBBS², Seth Sweetser, MD¹, Frank A. Sinicrope, MD¹. P3632 - Colon Carcinomas Shown to Arise From Sessile Serrated Lesions (SSLs) at Pathology Show Frequent Dysplasia and Features of the Serrated Neoplasia Pathway, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.