Nuclear Immunoreactivity of β-Catenin Is Associated with Higher Expression of AMACR, Lower Rate of Nodal Metastasis, and Left-Side Location in Surgically Resected Deeply Invasive Colonic Cancer
Keith K Lai, Wei Jiang, Paula Carver, Angen Liu, Huihui Liu, Bin Zhang, Hao Xie, Xiuli Liu. Cleveland Clinic, Cleveland, OH; Thomas Jefferson University, Philadelphia, PA
Background: Dysregulation of the APC/Wnt/β-catenin signaling pathway is a key event in colonic carcinogenesis. Recently, alpha-methylacyl-CoA racemase (AMACR), a dietary enzyme involved in the β-oxidation of branched-chain fatty acids, has been reported to be upregulated in colonic adenocarcinomas. However, the mechanism underlying this upregulation remains unexplored. We aim to link AMCAR expression in colon cancer with β-catenin nuclear translocation, an indicator of APC/Wnt signaling pathway dysregulation.
Design: Tissue microarrays (TMA) were constructed from 112 cases of surgically resected, deeply invasive (T3 and T4), sporadic colonic adenocarcinomas and used for immunohistochemistry with stains for β-catenin and AMACR. Any amount of nuclear staining for β-catenin, and any amount of cytoplasmic staining for AMACR, were considered positive. Continuous and categorical data were analyzed using the student t test and chi-square test, respectively.
Results: Fifty of the 112 tested colonic adenocarcinomas had nuclear β-catenin staining. Whereas 82% (41 of 50) of these deeply invasive carcinomas with nuclear β-catenin staining also expressed AMACR, AMACR was expressed in only 50% (31 of 62) of carcinomas lacking nuclear β-catenin (Table 1; p = 0.00044). Nuclear β-catenin expressing carcinomas also had a lower rate of nodal metastasis than tumors lacking nuclear β-catenin (32% vs. 58.4%; p = 0.00357). Lastly, nuclear β-catenin positive carcinomas were more likely to be left-sided (70.2% vs. 46.5%; p = 0.045).
|Β-Catenin nuclear stain (50)||Lack of Β-Catenin nuclear stain (62)||p value|
|AMACR positive cases (%)||41 (82%)||31 (50%)||0.00044|
|Age, mean (SD), yrs||71.7 (10.2)||70.5 (11.2)||0.54|
|Male (%)||32 (64%)||36 (46.7%)||0.07|
|Left side (%)||33 (70.2%)||27 (46.5%)||0.014|
|Nodal metastasis (%)||16 (32%)||45 (58.4%)||0.00357|