Objectives: 
Using immunohistochemistry for MCMs and CGA:
Examine the proliferative compartment of SPs
Assess neuroendocrine cell population in SPs
Goal: Identify potential trends in the proliferative and the neuroendocrine cell compartments in SP progression compared to the background normal mucos

Boman, MD, PhD, Bruce M.

Fortuna, MD, Danielle

Palazzo, MD, Juan P.

Name not available

MCM2 and chromogranin are markers of serrated polyp progression

Jefferson Digital Commons

Thomas Jefferson UniversityJefferson Digital CommonsPathology, Anatomy and Cell Biology Resident'sPostersDepartment of Pathology, Anatomy and CellBiology2015MCM2 and chromogranin are markers of serratedpolyp progressionDanielle Fortuna, MDDepartment of Surgery, Thomas Jefferson University, danielle.fortuna@jefferson.eduBruce M. Boman, MD, PhDThomas Jefferson University, Bruce.Boman@jefferson.eduJuan P. Palazzo, MDThomas Jefferson University, Juan.Palazzo@jefferson.eduLet us know how access to this document benefits youFollow this and additional works at: http://jdc.jefferson.edu/pacbresidentpostersPart of the Medical Anatomy Commons, Medical Cell Biology Commons, and the MedicalPathology CommonsThis Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of ThomasJefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarlypublications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers andinterested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion inPathology, Anatomy and Cell Biology Resident's Posters by an authorized administrator of the Jefferson Digital Commons. For more information,please contact: JeffersonDigitalCommons@jefferson.edu.Recommended CitationFortuna, MD, Danielle; Boman, MD, PhD, Bruce M.; and Palazzo, MD, Juan P., "MCM2 andchromogranin are markers of serrated polyp progression" (2015). Pathology, Anatomy and CellBiology Resident's Posters. Paper 21.http://jdc.jefferson.edu/pacbresidentposters/21BackgroundSerrated polyp (SP) pathophysiology is of great interest, and examination of colonic stem cell (SC) differentiation and crypt cell proliferation can provide insight into the natural progression of SPs. In normal colonic mucosa, SCs can differentiate into neuroendocrine cells (NEC) that reside in the crypt-base stem cell niche. SCs also produce rapidly proliferating cells located in the proliferative compartment in the lower half of the crypt. Staining for minichromosome maintenance 2 (MCM2) protein, a component of the DNA helicase involved in the initiation of DNA replication, is a marker of cellular proliferation in all cell cycle phases. Chromogranin (CGA) is a marker of differentiated NECs. Using MCM2 and CGA, we examined these cell types in SPs: hyperplastic polyps (HP) and sessile serrated adenomas (SSA) with and without cytologic dysplasia.MethodsImmunohistochemistry was performed on 46 paraffin-embedded SPs (11 HPs, 31 SSAs, 4 SSAs with dysplasia) and sections of normal colon using anti-MCM2 antibody (Santa-Cruz, Dallas, TX; 1:200 dilution) and CGA (Dako, Carpinteria, CA; 1:10 dilution).  Staining positivity and distribution in both SP and adjacent normal colonic mucosa was assessed. Expected proliferation/differentiation patterns in normal colon: o positive nuclear MCM2 staining of the lower portion of the colonic crypto positive cytoplasmic CGA staining of scattered cells in the lower portion of the colonic cryptMCM2 demonstrated 3 major categories of staining: o expected/normal: staining limited to lower portion of crypt or slightly expandedo focal: non-continuous full crypt staining  o diffuse: continuous full crypt staining CGA demonstrated the following staining patterns: o present (individual scattered cells)  o absent (non-continuous or continuous)ResultsPatterns of MCM2 staining in SPs: 100% of HPs, SSAs, and SSAs with dysplasia showed some degree of positive MCM2 staining throughout the entire crypt (focal/diffuse  full crypt staining). Diffuse full crypt proliferation was seen in 100% of SSAs with dysplasia, 81% of SSAs, and 64% of HPs. Surface staining was focal/absent in all polyps. Patterns of MCM2 staining in background normal mucosa: When present, areas of histologically normal mucosa adjacent to SPs showed aberrant, full crypt staining of MCM2 in 100% of SSAs with dysplasia and 58% of SSAs. Adjacent normal mucosa of HPs showed the expected/normal pattern. Patterns of CGA staining in SPs: HPs and SSAs showed scattered CGA-positive cells in the lower crypt (>5 cells per crypt base). 100% of SSAs with dysplasia and a small subset of SSAs (30%), showed rare to absent CGA positive cells.ResultsGraphic and tabular representation of MCM2 and CGA staining patterns in SPsConclusionso Expansion of the proliferation compartment and neuroendocrine cell loss are components of SP development and progression.o HPs and SSAs show a similar proliferative profile. o Aberrant cell proliferation cell staining patterns in the normal colonic mucosa adjacent to SSAs with dysplasia (and a subset of SSAs) suggest that the colonic microenvironment may play a significant role in SP progression. o Continued exposure/stimulation from a particular microenvironment may promote SP formation and predisposition to malignancy. MCM2 and chromogranin are markers of serrated polyp progressionDanielle Fortuna MD1, Bruce Boman MD, PhD2, Juan P. Palazzo MD11Department of Pathology, Thomas Jefferson University Hospital, PA; 2Department of Medical Oncology, Thomas Jefferson University Hospital, PAObjectivesUsing immunohistochemistry for MCM2 and CGA:o Examine the proliferative compartment of SPso Assess neuroendocrine cell population in SPsGoal: Identify potential trends in the proliferative and the neuroendocrine cell compartments in SP progression compared to the background normal mucosaHPs SSAs SSAs with dysplasiaTable 1. Observed MCM2, CGA staining patternsInterpretation: SP progression may include extension of the proliferative compartment (orange and green), expansion of proliferative changes to surrounding normal mucosa (blue), and loss of NECs (purple). Diagram1. Observed MCM2 and CGA staining patterns. (Colors correspond to categories in Table1; circle size approximates relative proportion within given group.)Figure3. CGA, SSA with dysplasia shows rare to absent CGA positive cells.Figure2, MCM2. SSA with dysplasia (left) and adjacent normal mucosa (right) showing diffuse MCM2 staining. Figure1A-C, MCM2. Normal colonic mucosa (A) compared to full crypt staining in HP(B) and SSA (C). AB CNothing To Disclose – The authors of this abstract have indicated that they have no conflicts of interest that relate to the content of this abstract

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MCM2 and chromogranin are markers of serrated polyp progression

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