[677] 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).

Correlation of Β-catenin nuclear immunoreactivity with AMCAR expression, demographics and histologic tumor parameters in colonic adenocarcinoma
 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), yrs71.7 (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

Conclusions: Our results, for the first time, suggest that APC/Wnt/β-catenin pathway dysregulation may induce AMACR expression during colonic tumorigenesis. Further study is needed to explore the relationship between APC/Wnt/β-catenin pathway dysregulation and AMACR expression in colon cancer including early, superficially invasive adenocarcinomas (T1 and T2).
Category: Gastrointestinal

Wednesday, March 6, 2013 9:30 AM

Poster Session V # 86, Wednesday Morning


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