Morphologic and Immunohistochemical Characteristics of Colonic Serrated Polyps with Dysplasia
Kyle Viani, Kyoung Kim, Amitabh Srivastava, Robert Odze. Brigham and Women's Hospital, Boston, MA; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Background: The serrated pathway of colon carcinogenesis proposes that some cancers develop via a sessile serrated adenoma/polyp (SSA/P) or a traditional serrated adenoma (TSA)-dysplasia-carcinoma sequence. The types of dysplasia that arise in benign serrated polyps, their grading, morphologic and immunohistochemical characteristics are poorly defined. The aim of this study was to evaluate the morphologic and selected immunohistochemical characteristics of serrated polyps with dysplasia to better define neoplastic progression in serrated polyps.
Design: 99 serrated polyps (61 SSA/P, 40 with dysplasia, 21 with no dysplasia; 38 TSA all with dysplasia) were evaluated for the type (serrated, adenomatous) and grade (low and high) of dysplasia according to predetermined objective pathologic criteria. All polyps were stained immunohistochemically for p53, β-catenin, p16, MIB1, MUC6, and MLH1 and scored as either positive or negative in the various types and grades of dysplasia in each polyp. MIB1 was scored in the superficial third of the polyp and scored as grade 1= <25%, 2=25-50%, 3=≥50% positive cells.
Results: In TSA, p53 showed increasing positivity in low (27%), and high-grade dysplasia (80%) (P<0.05). Nuclear β-catenin was present in 13% and p16 in 18% of TSA, both with values similar in low and high-grade dysplasia. In contrast, p53 was rarely positive in SSA/P (3% in low grade dysplasia; 0% in high grade dysplasia). p16 and β-catenin were negative in all SSA/P with or without dysplasia. MLH1 staining was lost in 10% of dysplastic SSA/P but was intact in all grade of dysplasia in TSA. MIB1 staining in both TSA and SSA/P showed a significant increase with increasing grade of dysplasia (P<0.05). MUC6 stained the majority of TSAs (82%) and SSPs (93%). No significant differences in staining patterns were observed between polyps located in the left and right colon or between serrated and conventional adenomatous dysplasia in each polyp group.
Conclusions: Our grading system of dysplasia suggests that hyperproliferation, p53, β-catenin, and p16 play a role in the progression of neoplasia in TSAs, whereas these abnormalities are not important in the progression of SSA/P. Serrated and adenomatous dysplasia appear to develop via a similar molecular pathway and both types likely portend a similar risk of cancer progression.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 130, Tuesday Afternoon