Sessile Serrated Polyp / Adenoma

Supplemental Studies

MUC6 positive

At least focal staining of basal crypts in 100% of cases
Most staining seen in straight, regular crypts
Occasional staining in horizontal or dilated bases of crypts
Only rare staining in branched or basally serrated crypts
(Based on one report so far by Owens 2008, but Gibson 2011 finds considerable overlap with hyperplastic polyps)

	Ki67	CK20
Normal mucosa	Limited to basal ¼	Limited to surface
Hyperplastic polyp	Expanded to basal 1/3-1/2	Expanded to luminal 1/2-2/3
SSA	Patches of staining at all levels	Patches of staining at all levels
TSA	Mainly localized to ectopic crypts	Irregular staining of luminal surface
Usual adenoma	High overall	Random

(based on Torlakovic 2008)

Clear cell variant reported to be positive for hepatocyte nuclear factor-1Beta but sensitivity and specificity do not appear to be useful for diagnosis

Genotype is not useful for diagnosis but supportive of separate pathways for TSA and SSA

	Traditional Serrated Adenoma	Sessile Serrated Polyp / Adenoma
KRAS	50-80%	Minority (~0-10%)
BRAF	20-40%	Majority (~75%)
p53	Infrequent	Infrequent
APC	Infrequent	Infrequent
MSI	Can lead to MSI-L or MSS Serrated adenocarcinoma (SAca)	Can lead to MSI-H or L SAca
CpG island methylator phenotype (CIMP)	Primarily MGMT involvement in SAca	Primarily MLH1 involvement in SAca

(based on Makinen 2007, O’Brien 2006 and Weiland 2014)

Genotype suggests SSA may be a precursor of sporadic MSI high colorectal carcinomas (serrated carcinoma pathway)
- BRAF mutations and DNA hypermethylation in both
- Large (≥1 cm) SSA share marked predominance of right colon location with sporadic MSI high carcinomas
- Same genotype is frequent in small left sided lesions demonstrating some but not all of the histologic features of SSA
  - This suggests that size ≥1 cm and right side location should be required for the diagnosis to maintain its relevance to the serrated carcinoma pathway