Traditional serrated adenoma has two distinct genetic pathways for molecular tumorigenesis with potential neoplastic progression

Yoshihito Tanaka,Makoto Eizuka,Hiroo Yamano,Takayuki Matsumoto,Keisuke Kawasaki,Noriyuki Uesugi,Hiromu Suzuki,Tamotsu Sugai

doi:10.1007/s00535-020-01697-5

Yoshihito Tanaka, Makoto Eizuka + Show 6 more

Open Access

https://doi.org/10.1007/s00535-020-01697-5

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Abstract

BackgroundRecent studies have shown that traditional serrated adenoma (TSA) can be classified into BRAF and KRAS subtypes. Here, we examined the clinicopathological and molecular findings of 73 TSAs.Materials and methodsTSAs were subclassified into BRAF type (46 cases, type A) and KRAS type (27 cases, type B) and divided into polyp head (TSA component) and base (precursor component [PC]) to identify pathological and molecular differences between the two components. BRAF and KRAS mutations, microsatellite instability (MSI), and DNA methylation status of the TSA component and PC were analyzed. In addition, immunohistochemical expressions of annexin A10, MUC2, MUC5AC, MUC6, and CD10 were also examined. Finally, we compared endoscopic findings with histological features.ResultsWe classified type As into 31 type A1s with mutation of the corresponding PC (42.5%) and 15 type A2s without mutation of the PC (20.5%). None of the corresponding PCs without KRAS mutation were observed in type Bs. MSI was not detected in the TSAs examined. There were significant differences in the frequency of annexin A10 and MUC5AC expression between the three subtypes. Furthermore, we compared the TSA component with the corresponding PC to identify the progression mechanism between the two components. Methylation status played an important role in the progression of type A1 from the corresponding PC, unlike type A2 and type B. Finally, specific endoscopic findings were well correlated with distinct histological findings.ConclusionTSAs were heterogeneous tumors with two or three pathways to neoplastic progression.

Highlights

Materials and methods traditional serrated adenoma (TSA) is a rare type of serrated polyp that accounts for less than 1% of all colorectal polyps [1], TSA is thought to be an important type of colorectal polyp occasionally encountered in routine histopathological diagnosis [2, 3]
We examined a series of TSAs with BRAF or KRAS mutations, focusing on the molecular genetics associated with the serrated pathway, including annexin A10, mucin marker, and CD10 expression; DNA methylation status; and clinicopathological features
BRAF type was subclassified into type A1 with BRAF mutations in the precursor components (31 cases) and type A2 without BRAF mutations in the precursor components (15 cases); none of the corresponding precursor components without KRAS mutations were observed in type B

Summary

Introduction

Materials and methods traditional serrated adenoma (TSA) is a rare type of serrated polyp that accounts for less than 1% of all colorectal polyps [1], TSA is thought to be an important type of colorectal polyp occasionally encountered in routine histopathological diagnosis [2, 3]. According to traditional histological classification, serrated polyps are primarily classified into three subtypes, including hyperplastic polyps (HPs), TSA, and SSLs [7]. SSL is recognized as a type of precursor lesion for colorectal cancer (CRC) with a microsatellite instability (MSI)-high phenotype, whereas TSA is likely to progress into CRC with a microsatellite stable (MSS) phenotype [7,8,9,10]. Recent studies have shown that traditional serrated adenoma (TSA) can be classified into BRAF and KRAS subtypes. BRAF and KRAS mutations, microsatellite instability (MSI), and DNA methylation status of the TSA component and PC were analyzed. Keywords Annexin A10 Á BRAF mutation Á KRAS mutation Á DNA methylation Á Traditional serrated adenoma

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