[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
LocationHistologyKRASBRAFMSICIMP
IleumTSAG13DNegStableLow
JejunumTSAG12DNegStableNeg
IleumMPNegNeg--Neg
JejunumMPQ61ENegStableLow
DuodenumMP----MSI-L--
DuodenumTSANegNegStable--
DuodenumSSAG12DNegStableLow
DuodenumMPG12DNeg----
DuodenumHPNegV600EStable--
StomachTSA with fundic gland polypQ61HNegStableNeg
StomachHPNegNegStableLow
StomachMPG12DNegMSI-HHigh
StomachMPNegNeg----
AmpullaTSAG12ANegStableNeg
AmpullaTSANegNegStableLow
--, 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

 

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