Prognostic value of carcinoembryonic antigen distribution in tumor tissue of colorectal carcinoma.

Context: Carcinoembryonic antigen (CEA) can be detected in colorectal tumor tissue but its role in the survival of patients remains controversial.

Objective: To characterize the expression of tissue CEA using immunohistochemical staining in colorectal tumors and to analyze the relationship between this finding and preoperative plasmatic level of CEA, morphologic features and survival of patients operated with curative intent for colorectal carcinoma.

Method: Forty-seven patients were included in the study: 18 (38.3%) males and 29 (61.7%) females, with a mean age of 67.8 +/- 9.7 years (37 to 84 years). Immediately before laparotomy, pre-operative serum levels of CEA were obtained where normal levels were considered < or =2.5 ng/mL for non-smokers, and < or =5.0 ng/mL for smokers. CEA immunohistochemical studies were carried out using anti-human CEA monoclonal mouse antibody. The expression of immunostaining for each neoplasia was classified according to the pattern of CEA tissular distribution into apical or cytoplasmic. The variables considered for the statistical analysis were plasmatic preoperative CEA level, location of the lesion within the large intestine, lesion diameter, lymph node involvement, Duke's classification, vein invasion, grade of cellular differentiation, survival and pattern of CEA tissular distribution. The statistical models utilized were Spearman's correlation and the Mann-Whitney, Kruskal-Wallis and Student t tests. Patients' survival was analyzed using the Kaplan-Meier method.

Results: The mean preoperative CEA value was 15.4 +/- 5.5 ng/mL (0.2 to 92.1 ng/mL). The neoplasm was located in the colon in 29 (61.7%) and in the rectum in 18 (38.3%) patients. Eight (17.0%) patients were classified as Duke's stage A, 22 (46.8%) as stage B and 17 (36.2%) as stage C. On immunohistochemical studies, the pattern of CEA tissular distribution was apical in 33 (70.2%) patients and cytoplasmic in 14 (29.8%) patients. Patients with apical patterns presented a mean sera CEA level of 15.5 +/- 6.5 ng/mL while those with cytoplasmic pattern attained a mean sera CEA level of 15.1 +/- 7.3 ng/mL, with no significant difference between these values (P = 0.35). Apical distribution of CEA occurred in 6 (12.8%) Duke A, 18 (38.2%) Duke B and 9 (12.2%) Duke C patients, while cytoplasmic CEA tissular distribution was observed in 2 (4.2%) Duke A, 3 (6.4%) Duke B and 9 (19.1%) Duke C patients. Patients with Duke B neoplasms presented significantly more apical CEA tissular distribution patterns (P = 0.049) than subjects with cytoplasmic CEA tissular patterns. The apical CEA tissular distribution pattern in neoplasms was significantly more frequent in neoplasms with no lymph node compromise compared to the cytoplasmic pattern (P = 0.50). However, no significant differences were seen between apical and cytoplasmic CEA tissular distribution patterns in terms of colon or rectal site (P = 0.21), lesion diameter across greatest axis (P = 0.19), vein invasion (P = 0.13) or degree of cellular differentiation (P = 0.19). Of the 47 patients operated, 33 (70.2%) survived for more than 5 years where mean survival was 31.1 +/- 5.6 months. Survival between patients with apical and cytoplasmic CEA tissular distribution showed no significant difference (P = 0.38).

Conclusions: Although the apical distribution pattern of CEA was significantly more frequent in more advanced stages of Duke's classification, the CEA tissular distribution presented no relationship with serum CEA levels, morphological features of the neoplasm or survival of patients undergoing curative colorectal carcinoma resection.