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13.06.2020 | Original Article—Alimentary Tract | Ausgabe 9/2020 Open Access

Journal of Gastroenterology 9/2020

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

Zeitschrift:
Journal of Gastroenterology > Ausgabe 9/2020
Autoren:
Yoshihito Tanaka, Makoto Eizuka, Noriyuki Uesugi, Keisuke Kawasaki, Hiroo Yamano, Hiromu Suzuki, Takayuki Matsumoto, Tamotsu Sugai
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00535-020-01697-5) contains supplementary material, which is available to authorized users.

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Abstract

Background

Recent 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 methods

TSAs 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.

Results

We 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.

Conclusion

TSAs were heterogeneous tumors with two or three pathways to neoplastic progression.

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Zusatzmaterial
Supplementary file1 Supplementary Fig. Representative endoscopic images and histological features of type A1, type A2, and type B TSAs. a, Endoscopic images of the TSA component of type A1 TSAs. The type IV-serrated pit pattern is evident (Indigo carmine staining). b. Endoscopic images of the precursor component of type A1 TSAs. The type II pit pattern is clearly demonstrated (Indigo carmine staining). c. The type IV-serrated pits of the lesions were histological features of TSAs. d. The type II pits of the lesion were histological features of microvesicular hyperplastic polyps. e. Endoscopic images of the TSA component of type A2 TSAs. The type IV-serrated pit pattern is evident (Indigo carmine staining). f. Endoscopic images of the precursor component of type A2 TSAs. The type II pit pattern is clearly demonstrated (Indigo carmine staining). g. The type IV-serrated pits of the lesion were a histological feature of TSA. h. The type II pits of the lesion were a histological feature of microvesicular hyperplastic polyps. i, Endoscopic images of the TSA component of type B TSAs. Type IV-serrated pit pattern is evident (Indigo carmine staining). j. Endoscopic images of the precursor component of type B TSAs. The type II-Long pit pattern is clearly demonstrated (Indigo carmine staining). k. The type IV-serrated pits of the lesions were a histological feature of TSA. l. The type II-Long pits of the lesions were a histological feature of superficially serrated adenoma (DOCX 18 kb)
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