Loss of E-cadherin independently predicts the lymph node status in colorectal cancer

The identification of biomarkers that improve risk stratification in patients with colorectal cancer (CRC) is still a challenge. The objective of our study was to identify independent protein markers as predictors of lymph node (N) stage in CRC.

Tumour specimens from 221 CRC patients were mounted onto a multiple-punch tissue microarray and evaluated for 21 tumour related factors and one host related factor involved in CRC carcinogenesis, namely β-catenin, E-cadherin, EGFR, pERK, RHAMM, pAKT, pSMAD2, p21, p16, Bcl-2, Ki-67, APAF-1, MST1, RKIP, VEGF, EphB2, MMP7, Laminin5γ2, MUC1, CDX2, caspase-3 as well as intra-tumoural and stromal CD8+ tumour infiltrating lymphocytes (iTILs and sTILs).

Node positive cancers showed significant losses for p21 (p = 0.026), Bcl-2 (p = 0.027), APAF-1 (p = 0.033), EphB2 (p = 0.006), E-cadherin (p < 0.001), RKIP (p = 0.019), CD8+ iTILs and sTILs (p < 0.001 and p = 0.008, respectively) and cytoplasmic MST1 (p = 0.014). Based on the area under the receiver operating characteristic curve (AUC) EphB2, E-cadherin, iTILs and sTILs were identified as potential predictors of N stage (AUC values >0.6), but only loss of E-cadherin was an independent predictor in multivariate analysis.

E-cadherin appears to be a strong predictor of N stage in CRC and should be considered in pre-operative and post-operative management of colon and rectal cancer patients.