Reduced E-Cadherin Expression and Enlargement of Cancer Nuclei Strongly Correlate with Hematogenic Metastasis in Colorectal Adenocarcinoma

Abstract

Synchronous and metachronous hematogenic metastases are frequently detected in patients with colorectal carcinoma. Once these metastases have developed, the prognoses of patients are poor. Previously, we reported that enlargement of cancer nuclei significantly correlated with metastatic potential of gastric cancer and hepatocellular carcinoma. Moreover, recently it has been reported that reduced expression of E-cadherin is associated with tumor metastasis. To evaluate the correlation between nuclear area (NA) of cancer cells and expression of E-cadherin, and to elucidate whether these factors correlate with clinical outcome in patients with colorectal carcinoma, 105 consecutive patients were investigated. In each case, the NAs of 600 cancer nuclei were analyzed by means of a computer-assisted image analysis system and E-cadherin expression was detected immunohistochemically by an anti-E-cadherin monoclonal antibody. The expression levels of E-cadherin were divided into three groups according to the percentages of E-cadherin-positive cells (level 0: positive cells < or = 50%, level 1: 50% < positive cells < or = 80%, level 2: positive cells > 80%). The mean NA of cancer cells in 105 tumors was 57 microm2. The NAs of cancer cells enlarged in proportion to the decrease of E-cadherin expression levels (level 0, n = 48, 62 microm2; level 1, n = 35, 57 microm2, level 2, n = 22, 46 microm2, P = 0.002). The 10-year survival rates decreased in proportion to the reduced E-cadherin expression levels (80% in level 2, 64% in level 1, and 42% in level 0, P = 0.004). Moreover, the 10-year survival rate of 54 patients with large NA tumors (< or = 54 microm2, 36%) was significantly poorer than that of 51 patients with small NA tumors (< 54 microm2, 80%, P < 0.001). The NA of cancer cells was recognized as an important predictor for prognosis and hematogenic metastasis. Although reduced E-cadherin expression was not recognized as the risk factor for hematogenic metastasis, 80% of patients who developed hematogenic metastasis had tumors with both enlarged cancer nuclei and reduced E-cadherin expression. Detection of NA of cancer cells and E-cadherin expression in patients with colorectal carcinoma may reveal important information for hematogenic metastasis.