A clinicopathological and molecular analysis of 200 traditional serrated adenomas

被引：131

作者：

Bettington, Mark L. ^{[1
,2
,3
]}

Walker, Neal I. ^{[2
,3
]}

Rosty, Christophe ^{[2
,3
,4
]}

Brown, Ian S. ^{[3
,5
]}

Clouston, Andrew D. ^{[2
,3
,5
]}

McKeone, Diane M. ^{[1
]}

Pearson, Sally-Ann ^{[1
]}

Klein, Kerenaftali ^{[6
]}

Leggett, Barbara A. ^{[1
,2
,7
]}

Whitehall, Vicki L. J. ^{[1
,2
,8
]}

机构：

[1] QIMR Berghofer Med Res Inst, Conjoint Gastroenterol Lab, Brisbane, Qld 4006, Australia

[2] Univ Queensland, Sch Med, Brisbane, Qld, Australia

[3] Envoi Specialist Pathologists, Brisbane, Qld, Australia

[4] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Carlton, Vic 3053, Australia

[5] Pathol Queensland, Dept Anat Pathol, Brisbane, Qld, Australia

[6] QIMR Berghofer Med Res Inst, Stat Unit, Brisbane, Qld 4006, Australia

[7] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia

[8] Pathol Queensland, Dept Chem Pathol, Brisbane, Qld, Australia

来源：

MODERN PATHOLOGY | 2015年 / 28卷 / 03期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

CPG ISLAND METHYLATION; MICROSATELLITE-INSTABILITY; BRAF MUTATION; PREVALENCE; COLORECTUM; PHENOTYPE; PATHWAY; POLYPS; ADENOCARCINOMAS; POLYPECTOMY;

D O I：

10.1038/modpathol.2014.122

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

The traditional serrated adenoma is the least common colorectal serrated polyp. The clinicopathological features and molecular drivers of these polyps require further investigation. We have prospectively collected a cohort of 200 ordinary and advanced traditional serrated adenomas and performed BRAF and KRAS mutational profiling, CpG island methylator phenotype analysis, and immunohistochemistry for a panel of 7 antibodies (MLH1, beta-catenin, p53, p16, Ki67, CK7, and CK20) on all cases. The mean age of the patients was 64 years and 50% were female. Of the polyps, 71% were distal. Advanced histology (overt dysplasia or carcinoma) was present in 19% of cases. BRAF mutation was present in 67% and KRAS mutation in 22%. BRAF mutant traditional serrated adenomas were more frequently proximal (39% versus 2%; P <= 0.0001), were exclusively associated with a precursor polyp (57% versus 0%; P <= 0.0001), and were more frequently CpG island methylator phenotype high (60% versus 16%; P <= 0.0001) than KRAS mutant traditional serrated adenomas. Advanced traditional serrated adenomas retained MLH1 expression in 97%, showed strong p53 staining in 55%, and nuclear /1-catenin staining in 40%. P16 staining was lost in the advanced areas of 55% of BRAF mutant traditional serrated adenomas compared with 10% of the advanced areas of KRAS mutant or BRAF/KRAS wildtype traditional serrated adenomas. BRAF and KRAS mutant traditional serrated adenomas are morphologically related but biologically disparate polyps with distinctive clinicopathological and molecular features. The overwhelming majority of traditional serrated adenomas retain mismatch repair enzyme function indicating a microsatellite-stable phenotype. Malignant progression occurs via TP53 mutation and Wnt pathway activation regardless of mutation status. However, CDKN2A (encoding the p16 protein) is silenced nearly exclusively in the advanced areas of the BRAF mutant traditional serrated adenomas. Thus, the BRAF mutant traditional serrated adenoma represents an important precursor of the aggressive BRAF mutant, microsatellite-stable subtype of colorectal carcinoma.

引用

页码：414 / 427

页数：14

共 42 条

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