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.
|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|