[776] Inflammatory Bowel Disease (IBD)-Associated and Sporadic Colorectal Adenocarcinoma Is Immunophenotypically Different

Hao Xie, Wei Jiang, Bonnie Shadrach, Paula Carver, Xiuli Liu. Cleveland Clinic, Cleveland, OH; Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA

Background: While sporadic and IBD-associated colorectal neoplasia has been shown to be a multistep process of progression from low-grade dysplasia, high-grade dysplasia, and invasive adenocarcinoma, morphologically, most lesions of these two entities are thought to be similar. Our recent studies (Jiang W et al., 2012; Liu X et al., 2012) revealed that IBD-associated colorectal adenocarcinoma (CAC) is morphologically different from sporadic microsatellite stable CAC and 54.5% of ulcerative colitis peri-pouch adenocarcinoma had expression of cytokeratin 7 (CK7), a cytokeratin, not normally expressed in large intestine. These findings prompted us to further investigate the immunophenotype of IBD-associated CAC.
Design: Tissue microarrays (TMA) consisting of 65 IBD-related CACs [duplicate cores (2 mm in diameter) from each tumor] and 135 sporadic CACs were constructed and used for immunohistochemistry for CK7, CK20, p53, β-catenin, and a-methylacyl-CoA racemase (AMACR). Presence of immunoreactivity in ³ 15% and any cancerous nuclei is considered positive for p53 and β-catenin, respectively. AMACR was graded as 0 (none), 1 (weak), and 2 (strong) according to the stain intensity. Categorical data were analyzed using the chi-square test. A p value < 0.05 was considered statistically significant.
Results: The results are shown in Table 1.

Table 1. Immunophenotype of sporadic CAC and IBD-associated CAC
 Sporadic CAC (n=135)IBD-associated CAC (n=68)p value
# of cases with CK7 positivity (%)8 (5.9%)37 (54.4%)<0.00001
# of cases with CK20 positivity (%)107 (79.9%)64 (95.5%)0.006
# of cases with p53 positivity (%)60 (44.4%)39 (60%)0.049
# of cases with ß-catenin nuclear immunoreactivity (%)50 (39.4%)7 (10.4%)0.00002
# of cases with strong AMACR positivity (%)52 (38.5%)14 (21.6%)0.024
CAC: colorectal adenocarcinoma; IBD: inflammatory bowel disease; strong AMACR stain: stain intensity of 2.


Conclusions: Expression of CK7 and lack of β-catenin nuclear immunoreactivity are quite unique to IBD-associated CACs. While IBD-associate CAC has slightly higher rates of p53 immunoreactivity and CK20 expression, it is less likely to show strong AMACR expression. The underlying mechanism leading to this different immunophenotye remains to be determined. Collectively, our previous morphological study (Liu X. et al., 2012) and the current study strongly suggest that IBD-associated CAC and sporadic CAC are histomorphologically and immunophenotyically different.
Category: Gastrointestinal

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 137, Tuesday Afternoon

 

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