Open AccessMyeloperoxidase immunohistochemistry as a measure of disease activity in ulcerative colitis: Association with ulcerative colitis‐colorectal cancer, tumor necrosis factor polymorphism and RUNX3 methylation
Author(s) -
GarrityPark Megan,
Loftus Edward V.,
Sandborn William J.,
Smyrk Thomas C.
Publication year - 2012
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.21681
Subject(s) - ulcerative colitis , myeloperoxidase , medicine , colorectal cancer , inflammatory bowel disease , immunohistochemistry , pathology , colitis , tumor necrosis factor alpha , cancer , gastroenterology , immunology , inflammation , disease
Background: Patients with extensive, longstanding ulcerative colitis (UC), a disease of chronic colonic inflammation, are at risk for colorectal cancer (CRC). Elucidating the mechanism and fully characterizing the nature of this chronic inflammation offers the potential to identify those at greatest risk. We performed a case‐control study comparing histologic disease activity (HDA; neutrophils on hematoxylin and eosin [H&E]‐stained slides) with immunohistochemistry (IHC) directed against specific cell types. We correlated IHC results with data previously generated on methylation status of RUNX3 and single nucleotide polymorphisms (SNPs) in tumor necrosis factor alpha (TNF‐α). Methods: A nonadjacent, nonneoplastic section of bowel wall was identified for each UC‐CRC case. HDA was assessed for UC‐CRC cases ( n = 50) and UC‐controls ( n = 50). Sections were immunostained using antibodies against macrophages (CD68), neutrophils/monocytes (myeloperoxidase, MPO), and T cells (CD3). Slides were scored using ImageJ and results reported as the percent area positive for each marker. Results: HDA did not correlate with infiltrate levels as measured by IHC and increasing HDA was inversely related to UC‐CRC risk. Conversely, the percent area positive for CD68 and MPO was significantly elevated in UC‐CRC cases versus controls ( P = 0.04 and < 0.0001, respectively). In areas designated inactive, MPO staining remained significantly higher in UC‐CRC cases versus controls ( P = 0.002). Increased MPO staining was associated with methylation of RUNX3 and the TNF‐α −308G>A SNP. Conclusions: HDA is less sensitive than IHC and may underestimate inflammatory cell populations associated with UC‐CRC. The epigenetic/genetic associations related to elevated MPO staining in UC‐CRC may offer new methods for risk stratification and adjunctive screening tools. (Inflamm Bowel Dis 2011;)