Is Proximal Microvesicular Serrated Polyp the Precursor of Sessile Serrated Adenoma of the Colon?
H Xu, S Yang, O Adjapong, MJ O'Brien. Boston University School of Medicine, Boston, MA
Background: Sessile serrated adenoma (SSA) is a prevalent, mainly proximal, colonic lesion that is a key nexus in the serrated polyp pathway to carcinoma. Whether SSA is a unique lesion de novo or represents progression from a precursor hyperplastic polyp (microvesicular variant - MVSP) is controversial. The aim of this study is to evaluate the degree of concordance of mucin core protein expression, BRAF oncogene mutation and CpG island methylation (CIM) status between proximal MVSP and SSA.
Design: 35 endoscopically resected serrated polyps were selected: 25 MVSP (11 proximal and 14 distal) and 10 SSA, classified histologically according to the criteria of Torlakovic et al. Immunohistochemistry staining for MUC2 and MUC6 was performed; staining intensity for cytoplasmic MUC2 and ectopic expression of MUC6 was documented. DNA was extracted from all 35 polyps and KRAS codon 12, 13 mutations and BRAFV600E mutation were assayed. 15 genetic markers for CIM (p16, hMLH1, MGMT, MINT1, MINT2, SOCS1, Neurog1, RUNX3, IGF2, CACNA11G, SFRPS, RASSF2A, Reprimo, 30ST2 and HPP1) were assayed by methylation specific PCR. Groups were compared using Fisher's Exact and U-Mann Whitney tests as appropriate.
Results: All MVSP and SSA polyps shared the common histological features of serrated crypts and microvesicular mucin in cells of the upper crypt. The SSAs were selected on the basis of altered architecture of the basal crypts with inverted T or L-shape crypts. 23 of 25 MVSP (92%) and 8 of 10 (80%) SSA showed BRAF mutation. MUC2 expression was increased in all categories. Ectopic expression of MUC6 was found in 5/9 (55.6%) of the proximal MVSP (p=0.018) and 5/8 (62.5%) of the proximal SSA (p=0.01) compared to 1/14 (7.1%) of distal MVSP. Of the 15 CIMP markers assayed, the median CIM score was 8, 13 and 4 for the proximal MVSP, SSA and the distal MVSP respectively. CIM score of proximal MVSPs and proximal SSAs were significantly higher than those of distal MVSPs (p<0.001, p=0.001).
Conclusions: Concordance between histologic features, BRAF mutation, mucin phenotype and CpG island methylation status support the hypothesis that proximal MVSP is the precursor of SSA.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 71, Tuesday Afternoon