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;)
1*Division of Experimental Pathology and Lab Medicine, Mayo Clinic, Rochester, Minnesota
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
3Division of Gastroenterology, University of California San Diego, La Jolla, California
4Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota
*200 First St. SW, Stabile 2‐50, Rochester, MN 55905
Received 16 December 2010; Accepted 17 January 2011
Published online 18 March 2011 in Wiley Online Library (wileyonlinelibrary.com).