E-cadherin and NEDD9 expression in primary colorectal cancer, metastatic lymph nodes and liver metastases

Abstract

In Croatia, colorectal cancer mortality rates in males are the third highest in Europe, after Hungary and Slovakia. The results for females rank Croatia in second place after Hungary. According to previous studies, the loss of E-cadherin expression and the higher expression of neural precursor cell-expressed developmentally downregulated 9 (NEDD9) are associated with a worse prognosis. The aim of the present study was to analyze the immunohistochemical expression of NEDD9 and E-cadherin as markers of metastatic potential using a tissue microarray. This retrospective study included 40 previously untreated patients, including 23 males and 17 females with a median age of 64.5 years (range 38-84), with colorectal cancer and synchronous liver metastases that underwent simultaneous colorectal and hepatic resection between January 1st 2006 and December 31st 2013, in the Clinical Hospital Center Sestre Milosrdnice (Zagreb, Croatia). The most frequent tumor stage was T3, while the most frequent nodal stage was N1. Microvascular invasion was present in 37.5% of patients, while perineural invasion was observed in 30% of patients. The immunohistochemical staining index of E-cadherin was highly positive in 87.5% samples of colorectal cancer, 67.7% of lymph nodes and 77.5% of liver metastases. In the primary tumor, highly positive NEDD9 expression was identified in 22.5% of patients. In lymph nodes, it was identified in 35.5% of patients, while in the liver, it was identified in 30% of patients. Significant positive correlations were observed between the percentage of positive lymph nodes and the immunohistochemical staining index of E-cadherin (ρ=0.372; P=0.039) and NEDD9 (ρ=0.451; P=0.011) in lymph nodes. After the conclusion of the study, 55% of the patients succumbed. No significant differences in survival rates were identified regarding the expression of E-cadherin and NEDD9 in the primary tumor, metastatic lymph nodes and liver metastases. Due to the small sample size and the negative results obtained, further research is required to implement these parameters as prognostic factors.

Keywords: E-cadherin; colorectal cancer; immunohistochemistry; liver metastases; neural precursor cell-expressed developmentally downregulated 9; survival.

Figure 1.

High intensity immunohistochemical expression of E-cadherin in (A) the primary tumor, (B) LN metastasis and (C) liver metastasis. High intensity immunohistochemical expression of neuronal precursor cell-expressed developmentally downregulated 9 in (D) the primary tumor, (E) LN metastasis and (F) liver metastasis. Magnification, ×200. LN, lymph node; E-cadherin, epithelial cadherin.

Figure 2.

Expression of E-cadherin and NEDD9 in the primary tumor, metastatic LNs and liver metastasis compared with the survival outcome, as demonstrated by Kaplan-Meier survival curves with P-values from the log-rank test. E-cad, E-cadherin; ISI, immunohistochemical staining index; LN, lymph node, NEDD9, neuronal precursor cell-expressed developmentally downregulated 9.