Loss of CDH1 Expression in Colorectal Cancer Is Independently Associated with Microsatellite Instability and Female Gender
KL Golden, Y Baba, CS Fuchs, S Ogino. Brigham and Women's Hospital/Harvard Medical School, Boston, MA; Dana-Farber Cancer Institute, Boston, MA
Background: E-cadherin (CDH1) is important for maintaining the adhesive properties of epithelial cells, while its loss may contribute to the invasive properties observed in colorectal cancers. No study has comprehensively investigated the association of CDH1 loss in colorectal cancers with clinical, prognostic, pathologic, and molecular features, including microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP).
Design: Among 525 colorectal cancers with clinical outcome data, we detected loss of CDH1 membrane expression in 281 (54%) tumors by immunohistochemistry. We analyzed for CIMP by real-time PCR, and BRAF, KRAS, and PIK3CA mutations and LINE-1 methylation by Pyrosequencing.
Results: In multivariate logistic regression analysis with a stepwise selection procedure, CDH1 loss was significantly associated with female gender and MSI-high (Table 1), but not with age at diagnosis, body mass index, family history of colorectal cancer, tumor location, stage, tumor grade, mucinous or signet ring cell components, CIMP, BRAF, KRAS, PIK3CA, LINE-1 hypomethylation, p53, or COX-2. Compared to patients with CDH1-expressing colon cancers, those with CDH1-lost colon cancers showed a non-significant tendency for a high overall mortality (Figure 1) [hazard ratio 1.28; 95% CI, 0.99-1.66].
|Variables in the final model for CDH1 loss||Multivariate OR (95% CI)||P value|
|Female gender (vs. male gender)||1.89 (1.28-2.81)||0.0014|
|MSI-high (vs. MSI-low/MSS)||1.89 (1.12-3.21)||0.017|
|Mucinous component (>0% vs. 0%)||1.54 (1.00-2.39)||0.053|
|Signet ring cell component (>0% vs. 0%)||2.19 (0.92-5.20)||0.077|
|Stage IV (vs. stage I-III)||1.53 (0.88-2.67)||0.14|
|PIK3CA mutation||0.66 (0.36-1.21)||0.18|