Defining Crohn's Disease by Immunohisotchemistry and Histology: The Role of Metalloproteinase 3 and Its Inhibitor in Isolated Chronic Ileitis
AA Petrolla, L Zhang, W Xin. University Hospital Case Medical Center, Cleveland, OH; Case Western Reserve University, Cleveland, OH; Nanjing Gulou Hospital, Nanjing, Jiangsu, China
Background: The pathogenesis behind Crohn's disease is mutifactorial. Contributing aspects include an imbalanced inflammatory process, disorders of mucosal repair, genetic susceptibility, and bacterial infection. The extracellular matrix in the lamina propria of the gastrointestinal tract maintains the normal mucosal structure. The family of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are responsible for degrading the extracellular matrix. Many of the MMPs and TIMPs have been found to be expressed in ulcerated areas of Crohn's disease. Clinically, it is important to differentiate isolated ileitis caused by Crohn's disease from ileitis due to other causes, especially ileitis due to non-steroid anti-inflammatory drugs. In this study, we will determine if immunostaining with MMP3 and TIMP1 can help differentiate ileitis of Crohn's disease from ileitis due to other causes.
Design: Forty-six consecutive cases of isolated ileitis of the terminal ileum were retrieved. Biopsies were reviewed and included in the study provided the patient had no previous history of inflammatory bowel disease, and the biopsy showed terminal chronic ileitis without accompanying chronic colitis. The diagnostic criteria of chronic ileitis included crypt distortion, plasmacytosis in lamina propria, ulceration, and/or pyloric gland metaplasia. Clinical follow-up was up to 3.5 years.
Results: Among these 46 patients, 54% (25/46) of the patients had confirmed Crohn's disease during 3.5 years follow-up. By immunohistochemistry, 88% and 88% of those ileitis caused by Crohn's disease showed expressions of MMP3 and TIMP1,respectively, comparing to 24% and 19% in those ileitis caused by non Crohn's disease.
Table 1: The Expressions of MMP3 and TIMP1 in Ileitis
|MMP3+, TIMP1+||MMP3+, TIMP1-||MMP3-, TIMP1+||MMP3+, TIMP1-||Total|
Conclusions: Matrix metalloproteinase 3 (MMP3) and its tissue inhibitor (TIMP1) are expressed in isolated ileitis caused by Crohn's disease, with a sensitivity of 96% and specificity of 64% if either MMP3 or its inhibitor (TIMP1) is expressed, while the sensitivity will be decreased to 88% and specificity will be increased to 86% if both MMP3 and TIMP1 expressed. The utilization of immunostains of MMP3 and TIMP1 on isolated ileitis could help early diagnosis of Crohn's disease.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 62, Wednesday Morning