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Published in: Journal of Gastroenterology 9/2020

Open Access 01-09-2020 | Original Article—Alimentary Tract

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

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

Published in: Journal of Gastroenterology | Issue 9/2020

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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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Literature
3.
go back to reference Snover DC, Jass JR, Fenoglio-Preiser C, et al. Serrated polyps of the large intestine: a morphologic and molecular review of an evolving concept. Am J Clin Pathol. 2005;124:380–91.CrossRef Snover DC, Jass JR, Fenoglio-Preiser C, et al. Serrated polyps of the large intestine: a morphologic and molecular review of an evolving concept. Am J Clin Pathol. 2005;124:380–91.CrossRef
4.
go back to reference Longacre TA, Fenoglio-Preiser CM. Mixed hyperplastic adenomatous polyps/serrated adenomas. A distinct form of colorectal neoplasia. Am J Surg Pathol. 1990;14:524–37.CrossRef Longacre TA, Fenoglio-Preiser CM. Mixed hyperplastic adenomatous polyps/serrated adenomas. A distinct form of colorectal neoplasia. Am J Surg Pathol. 1990;14:524–37.CrossRef
5.
go back to reference Torlakovic E, Snover DC. Serrated adenomatous polyposis in humans. Gastroenterology. 1996;110:748–55.CrossRef Torlakovic E, Snover DC. Serrated adenomatous polyposis in humans. Gastroenterology. 1996;110:748–55.CrossRef
6.
go back to reference Torlakovic EE, Gomez JD, Driman DK, et al. Sessile serrated adenoma (SSA) vs traditional serrated adenoma (TSA). Am J Surg Pathol. 2008;32(1):21–9 (Erratum in: Am J Surg Pathol. 2008;32:491).CrossRef Torlakovic EE, Gomez JD, Driman DK, et al. Sessile serrated adenoma (SSA) vs traditional serrated adenoma (TSA). Am J Surg Pathol. 2008;32(1):21–9 (Erratum in: Am J Surg Pathol. 2008;32:491).CrossRef
7.
go back to reference Pai RK, Mäkinen MJ, Rosty C. Colorectal serrated lesions and polyps. In: The WHO Classification of Tumours Editorial Board, editors. WHO classification of tumours of the digestive system. 5th ed. Lyon: IARC press; 2019. pp. 163–9. Pai RK, Mäkinen MJ, Rosty C. Colorectal serrated lesions and polyps. In: The WHO Classification of Tumours Editorial Board, editors. WHO classification of tumours of the digestive system. 5th ed. Lyon: IARC press; 2019. pp. 163–9.
8.
go back to reference Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138:2088–100.CrossRef Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138:2088–100.CrossRef
11.
go back to reference Bettington ML, Chetty R. Traditional serrated adenoma: an update. Hum Pathol. 2015;46:933–8.CrossRef Bettington ML, Chetty R. Traditional serrated adenoma: an update. Hum Pathol. 2015;46:933–8.CrossRef
12.
go back to reference Bettington ML, Walker NI, Rosty C, et al. A clinicopathological and molecular analysis of 200 traditional serrated adenomas. Mod Pathol. 2015;28:414–27.CrossRef Bettington ML, Walker NI, Rosty C, et al. A clinicopathological and molecular analysis of 200 traditional serrated adenomas. Mod Pathol. 2015;28:414–27.CrossRef
13.
go back to reference Lee EJ, Choi C, Park CK, et al. Tracing origin of serrated adenomas with BRAF and KRAS mutations. Virchows Arch. 2005;447:597–602.CrossRef Lee EJ, Choi C, Park CK, et al. Tracing origin of serrated adenomas with BRAF and KRAS mutations. Virchows Arch. 2005;447:597–602.CrossRef
16.
go back to reference Kim JH, Rhee YY, Kim KJ, et al. Annexin A10 expression correlates with serrated pathway features in colorectal carcinoma with microsatellite instability. APMIS. 2014;122:1187–95.CrossRef Kim JH, Rhee YY, Kim KJ, et al. Annexin A10 expression correlates with serrated pathway features in colorectal carcinoma with microsatellite instability. APMIS. 2014;122:1187–95.CrossRef
17.
go back to reference Boland CR, Thibodeau SN, Hamilton SR, et al. National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–57.PubMed Boland CR, Thibodeau SN, Hamilton SR, et al. National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–57.PubMed
20.
go back to reference Sugai T, Eizuka M, Fujita Y, et al. Molecular profiling based on KRAS/BRAF mutation, methylation, and microsatellite statuses in serrated lesions. Dig Dis Sci. 2018;63:2626–38.CrossRef Sugai T, Eizuka M, Fujita Y, et al. Molecular profiling based on KRAS/BRAF mutation, methylation, and microsatellite statuses in serrated lesions. Dig Dis Sci. 2018;63:2626–38.CrossRef
27.
go back to reference Gonzalo DH, Lai KK, Shadrach B, et al. Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp. J Pathol. 2013;230:420–9.CrossRef Gonzalo DH, Lai KK, Shadrach B, et al. Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp. J Pathol. 2013;230:420–9.CrossRef
Metadata
Title
Traditional serrated adenoma has two distinct genetic pathways for molecular tumorigenesis with potential neoplastic progression
Authors
Yoshihito Tanaka
Makoto Eizuka
Noriyuki Uesugi
Keisuke Kawasaki
Hiroo Yamano
Hiromu Suzuki
Takayuki Matsumoto
Tamotsu Sugai
Publication date
01-09-2020
Publisher
Springer Singapore
Published in
Journal of Gastroenterology / Issue 9/2020
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-020-01697-5

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