Morphologic and molecular characterization of traditional serrated adenomas of the distal colon and rectum

Homer O. Wiland, Bonnie Shadrach, Daniela Allende, Paula Carver, John R. Goldblum, Xiuli Liu, Deepa T. Patil, Lisa A. Rybicki, Rish Pai

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration.

Original languageEnglish (US)
Pages (from-to)1290-1297
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume38
Issue number9
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Polyps
Rectum
Adenoma
Colon
Annexins
Methylation
CpG Islands
Mutation
antineoplaston A10
Villous Adenoma
Eosinophilia
Natural History
Immunohistochemistry

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Morphologic and molecular characterization of traditional serrated adenomas of the distal colon and rectum. / Wiland, Homer O.; Shadrach, Bonnie; Allende, Daniela; Carver, Paula; Goldblum, John R.; Liu, Xiuli; Patil, Deepa T.; Rybicki, Lisa A.; Pai, Rish.

In: American Journal of Surgical Pathology, Vol. 38, No. 9, 01.01.2014, p. 1290-1297.

Research output: Contribution to journalArticle

Wiland, HO, Shadrach, B, Allende, D, Carver, P, Goldblum, JR, Liu, X, Patil, DT, Rybicki, LA & Pai, R 2014, 'Morphologic and molecular characterization of traditional serrated adenomas of the distal colon and rectum', American Journal of Surgical Pathology, vol. 38, no. 9, pp. 1290-1297. https://doi.org/10.1097/PAS.0000000000000253
Wiland, Homer O. ; Shadrach, Bonnie ; Allende, Daniela ; Carver, Paula ; Goldblum, John R. ; Liu, Xiuli ; Patil, Deepa T. ; Rybicki, Lisa A. ; Pai, Rish. / Morphologic and molecular characterization of traditional serrated adenomas of the distal colon and rectum. In: American Journal of Surgical Pathology. 2014 ; Vol. 38, No. 9. pp. 1290-1297.
@article{c113df0c720448c2b614c7bf13816f1c,
title = "Morphologic and molecular characterization of traditional serrated adenomas of the distal colon and rectum",
abstract = "Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62{\%} of TSAs. Precursor lesions were seen in 24{\%} of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42{\%} and 48{\%} of polyps, respectively. GNAS mutations occurred in 8{\%} of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration.",
author = "Wiland, {Homer O.} and Bonnie Shadrach and Daniela Allende and Paula Carver and Goldblum, {John R.} and Xiuli Liu and Patil, {Deepa T.} and Rybicki, {Lisa A.} and Rish Pai",
year = "2014",
month = "1",
day = "1",
doi = "10.1097/PAS.0000000000000253",
language = "English (US)",
volume = "38",
pages = "1290--1297",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

TY - JOUR

T1 - Morphologic and molecular characterization of traditional serrated adenomas of the distal colon and rectum

AU - Wiland, Homer O.

AU - Shadrach, Bonnie

AU - Allende, Daniela

AU - Carver, Paula

AU - Goldblum, John R.

AU - Liu, Xiuli

AU - Patil, Deepa T.

AU - Rybicki, Lisa A.

AU - Pai, Rish

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration.

AB - Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration.

UR - http://www.scopus.com/inward/record.url?scp=84906793935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906793935&partnerID=8YFLogxK

U2 - 10.1097/PAS.0000000000000253

DO - 10.1097/PAS.0000000000000253

M3 - Article

C2 - 25127095

AN - SCOPUS:84906793935

VL - 38

SP - 1290

EP - 1297

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

IS - 9

ER -