[753] Serrated Polyps of the Extracolonic Gastrointestinal Tract: Histologic Findings and Genetic Alterations

Melissa W Taggart, Asif Rashid, Jeannelyn Estrella, Susan C Abraham. MD Anderson Cancer Center, Houston

Background: Serrated polyps are now recognized as precursors to a subset of colorectal carcinomas (CRC) and have been classified as hyperplastic (HP), sessile serrated adenoma (SSA), traditional serrated adenoma (TSA) and mixed adenomatous/serrated polyp (MP). HP and SSA frequently harbor BRAF mutations, while dysplastic lesions (TSA and MP) more commonly harbor KRAS mutations. CRC arising through the serrated neoplasia pathway often demonstrates high-level microsatellite instability (MSI-H) and CpG island methylator phenotype (CIMP). In contrast to serrated polyps of the colon, extracolonic serrated polyps are virtually undescribed and their genetic alterations are unknown.
Design: Fifteen serrated polyps from small bowel (n=9), stomach (n=4), and ampulla (n=2) were classified in accordance to serrated lesions of the colon as HP (n=2), SSA (n=1), TSA (n=6) and MP (n=6). Purified DNA from these lesions was subjected to pyrosequencing for BRAF (exons 11, 15) and KRAS (codons 12, 13, 61) mutations, immunohistochemistry and/or PCR for MSI status, and methylation-specific PCR for CIMP.
Results: Eleven (73%) of 15 serrated polyps were associated with invasive carcinoma, including 5 with mucinous features and 1 with signet ring cells. Oncogenic KRAS mutation was the most common abnormality, present in 8 of 14 cases (57%). MSI and CIMP were less common (Table 1). Only one polyp (duodenal HP) harbored a BRAF mutation (Fig 1).

TABLE 1. Extracolonic serrated polyps

Location	Histology	KRAS	BRAF	MSI	CIMP
Ileum	TSA	G13D	Neg	Stable	Low
Jejunum	TSA	G12D	Neg	Stable	Neg
Ileum	MP	Neg	Neg	--	Neg
Jejunum	MP	Q61E	Neg	Stable	Low
Duodenum	MP	--	--	MSI-L	--
Duodenum	TSA	Neg	Neg	Stable	--
Duodenum	SSA	G12D	Neg	Stable	Low
Duodenum	MP	G12D	Neg	--	--
Duodenum	HP	Neg	V600E	Stable	--
Stomach	TSA with fundic gland polyp	Q61H	Neg	Stable	Neg
Stomach	HP	Neg	Neg	Stable	Low
Stomach	MP	G12D	Neg	MSI-H	High
Stomach	MP	Neg	Neg	--	--
Ampulla	TSA	G12A	Neg	Stable	Neg
Ampulla	TSA	Neg	Neg	Stable	Low

--, insufficient DNA




Conclusions: In contrast to serrated polyps of the colon, serrated polyps in extracolonic locations have higher rates of dysplasia and more frequently contain invasive carcinoma. In our analysis, KRAS mutations were common in dysplastic serrated lesions and BRAF mutation was restricted to a nondysplastic duodenal HP.
Category: Gastrointestinal

Monday, March 19, 2012 1:00 PM

Poster Session II # 117, Monday Afternoon