Abstract 2603: What's more in serrated lesions: interobserver agreement and molecular features

Introduction: Serrated lesions are a heterogeneous group of lesions routinely evaluated with different morphologic subtypes, and colorectal carcinogenesis has been related to the understanding of the serrated pathway in these lesions. In this setting, BRAF V600E mutation has been demonstrated as a marker for the serrated carcinogenic evolution, while the mismatch repair protein (MMR) was recognized in a small subset of hyperplastic polyps. Design: This study aimed to evaluate the interobserver agreement among 6 pathologists in the morphological diagnosis of the serrated lesion according to WHO Classification; furthermore, the additional MMR (MLH1, PMS2, MSH2, MSH6) and BRAF V600E (VE1) mutation status were studied by immunohistochemistry and NGS analysis. Results: We evaluated 52 serrated lesions of the colon retrieved from our pathology archives in 2019. The cohort included 48 patients: 21 males and 27 females, with a mean age of 67 years (range 50-89), of which 77.1% were identified according to regional screening protocol. All hematoxylin and eosin slides were independently reviewed by each pathologist, who classified all samples according to the WHO Classification of Digestive System Tumor (Fleiss Kappa: 0.75). The immunohistochemical expression of MMR and BRAF was evaluated in 42 samples. Loss of MLH1 and PMS2 was recorded in one serrated sessile lesion (LSS) with dysplasia, but NGS analysis resulted negative. In contrast, BRAF V600E IHC resulted positive in 22 samples (52.4%), specifically in 5 hyperplastic polyps (71.4%), 10 LSS (66.6%), 5 LSS with dysplasia (45.5%) and 2 adenomatous polyps (100%), 1 TSA negative. All BRAF V600E IHC positive cases were confirmed by NGS analysis. Conclusion: To conclude, the interobserver agreement for morphological classification of serrated lesions resulted substantial; however, behind the morphological appearance, BRAF V600E resulted in predominant mutation in LSS and hyperplastic polyps, these observations confirmed the possibility to improve the classification with IHC BRAF V600E; especially for hyperplastic polyps, it may be crucial to identify precancerous lesions and different clinical management. Citation Format: Francesca Ambrosi, Costantino Ricci, Federico Chiarucci, Stefano Chilotti, Doriana Donatella Di Nanni, Angelo Gianluca Corradini, Maria Antonietta Cumiento, Dario De Biase, Michelangelo Fiorentino. What9s more in serrated lesions: interobserver agreement and molecular features [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2603.