title: MCM2 expression in serrated polyps demonstrates aberrant cellular proliferation.
abstract: In normal colonic epithelium, the proliferative zone is limited to the lower half of the colonic crypt. Evaluating the changes in the colonic epithelial proliferation can be useful in understanding pathophysiology of various diseases. Our aim was to investigate the proliferative compartment of serrated polyps (SPs) using MCM2, a protein involved in DNA replication, and assess for changes along the SP spectrum. Immunohistochemistry was performed on serrated polyps (16 microvesicular-type hyperplastic polyps (HP), 58 sessile serrated adenomas (SSA), 7 SSAs with dysplasia) and 6 sections of normal colon using anti-MCM2 antibody. Multiple sections of normal colon showed the following pattern for MCM2 and Ki-67 staining: positive nuclear staining of the lower half of the colonic crypts and/or slightly expanded to the lower two-thirds of the crypt. By MCM2, SPs show expansion of the proliferative compartments; 81.3% of HPs and 100% of SSAs showed some degree of full crypt MCM2 staining. SSAs with dysplasia showed consistent diffuse polyp staining. Aberrant staining in adjacent normal mucosa was also seen in SSAs with dysplasia and in a subset of non-dysplastic SSAs. By using MCM2, we show that serrated polyps exhibit changes in proliferation during progression along the pathway. HPs and SSAs show a similar highly proliferative profile. Aberrant proliferative cell staining patterns in adjacent normal colonic mucosa as seen in SSAs with dysplasia and a subset of SSAs suggest a field effect phenomenon. This indicates that changes in the colonic micro-environment may promote adenoma morphogenesis and predisposition to malignancy.
authors.affiliation: Department of Pathology, Thomas Jefferson University Hospital, PA 19107. Electronic address: danielle.fortuna@jefferson.edu.
authors.forename: Danielle
authors.initials: D
authors.lastname: Fortuna
authors.affiliation: Department of Medical Oncology, Thomas Jefferson University Hospital, PA 19107.
authors.forename: Bruce
authors.initials: B
authors.lastname: Boman
authors.affiliation: Department of Pathology, Thomas Jefferson University Hospital, PA 19107.
authors.forename: Raymond
authors.initials: R
authors.lastname: O'Neill
authors.affiliation: Department of Pathology, Thomas Jefferson University Hospital, PA 19107.
authors.forename: Juan
authors.initials: J
authors.lastname: Palazzo
mesh_terms: D018256:Adenomatous Polyps / Q000737:chemistry* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D049109:Cell Proliferation; D003106:Colon / Q000737:chemistry* / Q000473:pathology; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000473:pathology; D003111:Colonic Polyps / Q000737:chemistry* / Q000473:pathology; D004847:Epithelial Cells / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000473:pathology; D019394:Ki-67 Antigen / Q000032:analysis; D064111:Minichromosome Maintenance Complex Component 2 / Q000032:analysis*; D011230:Precancerous Conditions / Q000737:chemistry* / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2
keywords: Dysplasia; Immunohistochemistry; MCM2; Proliferation; SSA; Serrated polyps