Increased Expression of Sialyl Lewisx Antigen Correlates with Poor Survival in Patients with Colorectal Carcinoma: Clinicopathological and Immunohistochemical Study

We have previously shown that sialyl Lewisx antigen (sLex) (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAC-R) has an important functional role in defining the invasion and metastasis of human colorectal carcinoma. The results were derived from the clinical specimens obtained at surgery or experimental metastasis of human colon carcinoma variant expressing different levels of sLex in nude mice. In the present study, we immunohistochemically examined 132 human colorectal carcinomas for the expression of sLex to investigate whether this antigen expression could serve as a prognostic parameter. The tumors were divided into two groups: sLex positive and sLex negative. The incidence of sLex positive was correlated with the depth of tumor invasion, the presence of the lymph node metastasis, lymphatic invasion, and the disease stage. The difference was statistically significant (P = 0.0026; P = 0.0002; P = 0.003; P = 0.0013; respectively). Based on the data on 114 patients who underwent curative resections, incidence of the disease recurrence was assessed. The sLex-positive patients had higher incidence of recurrence in distant organs, especially in the liver, than that of the sLex-negative patients. The 5-year disease free survival rates of sLex-positive and -negative patients were 57.7 and 89.1%, respectively (P = 0.0002). The difference of 5-year overall survival rates between the two were also significant (sLex positive, 58.3%; sLex negative, 93.0%: P < 0.0001). By Cox multivariate analysis, sLex expression levels remained the best discriminant of disease-free survival (P = 0.035) and overall survival (P = 0.0081). These results suggest that increased expression of sLex is correlated with the extent of malignancy and high incidence of recurrence and consequently with survival of colorectal carcinoma patients. Thus sLex may prove to be a potent marker of recurrence in colorectal carcinoma patients.