Molecular and Immunohistochemical Features of Mixed Conventional Adenomatous-Serrated Colonic Polyps
Gerald F Reis, Sanjay Kakar, James P Grenert. UCSF, San Francisco, CA
Background: Colorectal cancer is the second leading cause of cancer-related death in the United States. The disease can be largely prevented by removal of adenomatous polyps. While common polyps show either conventional adenomatous or serrated features, mixed polyps with both patterns present a challenge for diagnosis and treatment. Not only is there ambiguity about how to classify mixed polyps but also uncertainty regarding their clinical significance. Better characterization of mixed polyps would permit more accurate follow-up of patients and further studies to determine their clinical importance. BRAF mutations are rare in conventional adenomas but common in serrated lesions. We tested distinct areas of conventional adenoma and serrated polyp in mixed polyps for BRAF mutations and MUC6 and Ki67 immunohistochemistry to determine whether the origin of these polyps was a conventional adenoma, a serrated polyp or a collision of both polyp types.
Design: The pathology records of three medical centers were searched for mixed polyps with conventional and serrated features. Cases were screened based on the final pathologic diagnosis and reviewed to confirm the present of a mixed morphological pattern. The two distinct morphological areas were microdissected and submitted for BRAFV600E mutational analysis. Immunohistochemistry for MUC6 and MIB-1 (Ki-67) was also performed.
Results: We identified 12 cases with mixed conventional adenoma and serrated polyp (traditional or sessile serrated adenoma (TSA, SSA), or hyperplastic polyp (HP)). BRAFV600E analysis demonstrated that both components of conventional/TSA polyps were negative for BRAF mutation (N=8) while both components of conventional/SSA polyps were positive (N=2). Mixed conventional/HP polyps were negative for BRAFV600E (N=2). Immunohistochemistry with MUC6 and MIB-1 demonstrated positivity for MUC6 only in SSA areas. MIB-1 positivity was largely basal in hyperplastic and SSA areas but more diffuse with apical enhancement in conventional and TSA areas.
Conclusions: The findings suggest that TSA features in conventional adenoma represent a metaplastic change in the conventional adenoma rather than dysplastic progression of a serrated precursor. The presence of BRAFV600E in both the conventional and serrated areas of conventional-SSA mixed polyps, along with MUC6 positivity in the SSA component, suggest dysplastic progression of SSA, which some studies have shown may have a more rapid progression to carcinoma than conventional adenoma. Our study demonstrates the utility of BRAF mutational analysis in the diagnosis of challenging adenomatous polyps with mixed pattern.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 129, Tuesday Afternoon