Time-dependency of the prognostic effect of carcinoembryonic antigen and p53 protein in colorectal adenocarcinoma

BACKGROUND, This study examined the prognostic information regarding the ri sk of postoperative tumor recurrence obtained by simultaneous determination of preoperative serum carcinoembryonic antigen (CEA) and immunohistochemic al expression of p53 protein in tumor tissue from patients with colorectal carcinoma. METHODS. A retrospective study of 174 patients (AJCC/UICC Stages I, II and III) was conducted. Serum CEA levels were determined by an enzyme-linked im munoadsorbent assay. Immunohistochemical expression of nuclear p53 protein was assessed in formalin fixed, paraffin embedded archival tumor tissue. Th e results of both factors were categorized by clinical and histopathologic variables. The relative prognostic significance of all factors with regard to disease free survival was assessed by Cox proportional hazards regressio n analysis. The stability of the predictive value of both markers was asses sed: 1) by splitting the follow-up into three intervals and performing sepa rate analyses for each period and 2) graphically by plotting the correspond ing cumulative hazards ratio along the follow-up. RESULTS. Eighty-two (47%) tumors manifested overexpression of p53 protein a nd 60 tumors (34.4%) exhibited elevated serum CEA levels (cutoff value of 5 ng/mL). p53 positive immunostaing and elevated CEA levels were associated with low cumulative disease free survival at 60 months' of follow-up, and p roved to have independent prognostic significance. Analysis performed in di fferent time periods of follow-up showed that the prognostic effect of both markers was not stable over time. The predictive significance of CEA and p 53 changed along the study periods. An elevated preoperative CEA level was an indicator of a high risk of recurrence only during the first 2 years aft er surgery (hazards ratio, 3.26; 95% confidence interval [95% CI], 1.6-6.42 ). The presence of p53 immunoreactivity in the primary tumor was an indicat or of a high risk of recurrence only after the first year of follow-up (haz ards ratio, 4.02; 95% CI, 1.68-9.6). CONCLUSIONS. The serum CEA level and expression of p53 protein provide comp lementary prognostic information. Time-dependency of the prognostic influen ce of both parameters should be taken into consideration when establishing postoperative predictive estimations. Cancer 2000;88:35-41, (C) 2000 Americ an Cancer Society.