The clinicopathologic significance of extranodal tumor extension in locally advanced (pT3) colorectal adenocarcinoma and its association with the loss of E-cadherin expression

Abstract

We investigated the clinicopathologic significance of extranodal tumor extension (ENTE) in locally advanced and prognostically inhomogeneous pT3 (pathologic T3) colorectal adenocarcinomas with regional lymph node metastasis. ENTE is defined as an interruption of the nodal capsule by tumor cells with extranodal growth. ENTE was observed in 46.3% of pT3 colorectal adenocarcinomas and was significantly associated with vascular invasion (P = 0.037, chi-square test), tumor deposit (P = 0.004, chi-square test) and high pN (pathologic N) stage (P = 0.002, chi-square test). An immunohistochemical study revealed that the loss of E-cadherin was significantly associated with ENTE (OR, 2.265; 95% CI, 1.008-5.086; P = 0.048). Kaplan-Meier survival analyses showed a significant difference between ENTE (+) and ENTE (-) groups for both cancer-specific survival (CSS) and recurrence-free survival (RFS) (P = 0.004 and P = 0.020, respectively, log-rank test). In the pN1a (single lymph node metastasis) subgroup, CSS and RFS were significantly shorter in patients with ENTE (P = 0.001 and P < 0.001, respectively, log-rank test). Comparing CSS and RFS according to pN stages and ENTE status, the survival curves of the pN1 group with ENTE were similar to those of the pN2 group without ENTE. ENTE is a useful prognostic factor for pT3 colorectal adenocarcinomas with regional lymph node metastasis, especially depending on the pN stages. The loss of E-cadherin expression may be an indicator of ENTE. Therefore, ENTE in colorectal adenocarcinoma should be considered in pN staging systems in the future.