CEA was initially described as a tumor and organ specific colorectal antigen, but later found by more sensitive methods in other tumors (stomach, pancreas, lung, breast) and in minor amounts in inflammatory, normal adult and fetal organs of the gastrointestinal tract. The main clinical application of CEA concerns its pretherapeutic and serial determination as circulating antigen in serum and other body fluids by means of CEA-specific, commercially available test kits. By clinical studies a significant correlation has been proven between the pretherapeutic serum CEA level and tumor stages and prognosis. Moreover, serial CEA level changes have been shown a valuable monitor following operation or during radio/chemotherapy anticipating and reflecting the clinical course of disease. In combination with newly established tumor markers, the main clinical indication for CEA determination in addition to colorectal cancer concerns monitoring of patients with stomach (+CA 72-4), lung (+NSE/SCC) and breast cancer (+CA 15-3/MCA).

Carcinoembryonic Antigen↗

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Significance of CEA determinations in patients with cancer of the colon-rectum and the mammary gland in comparison to physiological states in connection with pregnancy.

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Adult↗

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Value of human chorionic gonadotropin compared to CEA in discriminating benign from malignant effusions.

Human chorionic gonadotropin (HCG) is expressed in germ cell tumors and urothelial, breast, lung and colon cancers. The aim of the study was to investigate if the determination of HCG in comparison with CEA is able to discriminate between malignant and benign effusions. Effusion and partially serum samples of 61 patients with benign (g.i., heart/kidney isnuff.) and 116 patients with malignant diseases (g.i., gynec., lung, misc., CUP) were investigated. HCG was specifically determined by an IRMA using 2 monoclonal antibodies, CEA by a conventional double Ab RIA. Cytological staining was preformed using the Pappenheim-method on cytospin preparations. Significant differences (p < 0.001) were found for HCG between benign and malignant ascitic effusions with the best discrimination at 5 IU/l (ROC) and an overall sensitivity of 31.3% (spec. vs benign eff. 93.4%) increasing in subgroups from hematol. (5.8%) < misc. (31.3%) < gynec. (32.1%) < g.i. (36%) < lung (38.1%) to CUP (50%). CEA also showed significant differences between benign and malignant total and ascitic effusions, and weaker for the pleural subgroup (cutoff 9 ng/ml) with a total sensitivity of 44.6% (sp = 100%) increasing from misc. (30.8%) < lung (47.1%) < CUP (50%) < gynec. (60%) < g.i. (60.9%). Comparative cytology and TM determinations increased the positiverate of cytology (45.2%) to 58.3% for either cytology or HCG positive cases, or to 61.6% for either cytology or CEA positive cases. For the combined determination of cytologoy and HCG and CEA, the overall TM positive rate for 33 cytology-pos. cases was 78.8%, but in 40 cytology-negative cases 37.5% for TM positive cases. In conclusion HCG is useful in ascitic > pleural effusions with high specificity (90% at 5 IU/l) but low sensitivity of 31% increasing in g.i., lung and gynecologic cases, CEA a more general TM with higher sensitivity of 45% increasing in g.i., gynecologic and lung cases (sp. 100% at 9 ng/ml) both adding significantly to cytology-negative effusions.

Biomarkers, Tumor↗

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Use of serum PIVKA-II (DCP) determination for differentiation between benign and malignant liver diseases.

BACKGROUND: The concentration of Des-gamma-carboxy-prothrombin (DCP) or PIVKA-II has been described to be increased in patients with hepatocellular cancer, along with its elevation in vitamin K deficient states by warfarin or dicoumarol treatment. The aim of the study was to investigate its clinical value in HCC in comparison with alpha-fetoprotein. PATIENTS AND METHODS: Measurements were performed in duplicate in serum of 87 patients with benign (acute/chronic hepatitis B/C/autoimmune, liver cirrhosis B/C/alcoholic) and 154 patients with highly probable (CT, MRT imaging) or histologically proven HCC. Two commercial or research ELISA tests (1: Eitest MonoP-II, Eisai, Tokyo, Japan; 2: Asserachrom PIVKA-II, Stago, France) using murine monoclonal anti-PIVKA-II antibodies were used comparatively and compared with a laboratory-developed conventional AFP-RIA. RESULTS: By ROC analysis, a highly significant discrimination (p < 0.0001) was found at cutoffs of 0.09 AU/ml (Eisai) or 0.8 ng/ml (Stago) at a specificity of about 90% (Eisai: s = 78.6%, ppv = 0.92, npv = 0.70; Stago: s = 77.9%, ppv = 0.93, npv = 0.70) compared with the AFP-test at a cutoff of 45 ng/ml (sp = 91%, s = 58.4%, ppv = 0.92, npv = 0.55). A higher significant correlation was seen between both DCP tests in malignant (rS = 0.89, p < 0.0001) than benign groups (rS = 0.41, p < 0.001) and a lower correlation between the AFP and Eisai (rS = 0.27/0.36, p < 0.01) and Stago test for the malignant group (0.16; p < 0.05). CONCLUSION: DCP determination in serum/plasma adds significantly in the discrimination between benign and malignant liver diseases.

Adult↗

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Multivariate analysis of the prognostic value of CEA and CA 19-9 serum levels in colorectal cancer.

UNLABELLED: Carcinoembrionic Antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are the most commonly used tumor-associated antigens in the management of patients with colorectal cancer. The aim of this study was to evaluate the prognostic value of preoperative serum levels of CEA and/or CA 19-9 and the classical prognostic factors (age, sex, tumor infiltration and staging) in 495 patients. PATIENTS AND METHODS: The retrospective study was performed on frozen sera (stored at -70 degrees C) of patients with histologically proven colorectal cancer. Survival function estimates were calculated (Kaplan-Meier). The patients were separated into two groups according to the preoperative marker levels. Cut-off levels calculated at a specificity of 100% versus healthy individuals were used: < 4 ng/mL versus > or = 4 ng/mL for CEA and < 60 U/mL versus > or = 60 U/mL for CA 19-9. Survival curve differences were assessed using the log-rank-test. Mulivariate Cox's proportional hazard regression analysis was performed to examine the association between tumor marker levels and survival time. Classical prognostic factors such as age, sex, tumor infiltration, tumor stage (Dukes' classification) were included as covariants. The mantel-Haenszel method was used to assess the survival rate of patients with colorectal carcinoma and high versus low levels of tumor-associated antigens according to tumor stages. RESULTS: The Dukes' stages (log-rank chi-square = 231.9; p < 0.0001) represent the best prognostic factor besides the preoperative values of CA 19-9 (log-rank chi-square = 162.5). CEA shows a log-rank chi-square of 71.4. Thus, CEA and CA 19-9 can be used to discriminate two groups of patients with significantly different survival times (p < 0.0001). The importance of different parameters in providing additional prognostic information was evaluated by multivariate analysis. Only items of statistically significant prognostic relevance (univariate analysis) were used for this analysis. Estimated relative risks of death adjusted for tumor stage were 5.5 considering Dukes' stage A versus Dukes' stage B/C and Dukes' stage B/C versus Dukes' stage D, respectively, and an increasing relative risk of 27.5 for Dukes' stage A versus Dukes' stage D (p < 0.001). The relative risk for preoperative CA 19-9 serum concentrations (> or = 60 U/mL versus < 60 U/mL) was 2.3 (p < 0.001) and for preoperative CEA concentrations (> or = 4 ng/mL versus < 4 ng/mL) 1.4 (p < 0.07). For CEA the 2-year survival rates in the group of patients with preoperative serum concentrations > 4 ng/mL versus < 4 ng/mL and Dukes' stage D were 16% versus 38%, in Dukes' stage B/C 73% versus 91% and in Dukes' stage A 100% versus 98%. For CA 19-9 the 2-year survival rates in the group of patients with preoperative serum concentrations > or = 60 U/mL versus < 60 U/mL and Dukes' stage D were 10% versus 39%, whilst in Dukes' stage B/C 58% versus 87%. In the group of patients with Dukes' stage A with serum levels > or = 60 U/mL a 2-years survival rate of 100% was found. CONCLUSION: The postoperative Dukes' classification represents the best prognostic information besides the preoperative values of CA 19-9. The predictive information provided by preoperative CA 19-9 serum levels is independent from that obtained by the other factors investigated. Only Dukes' classification and CA 19-9 levels showed statistical significance (p < 0.001).

Biomarkers, Tumor↗

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Changes of thymidine kinase (TK) during adjuvant and palliative chemotherapy.

UNLABELLED: Thymidine kinase is involved in nucleic acid synthesis and is, therefore, considered to be an important proliferation tumor marker. For this reason, we monitored this marker in the course of colorectal cancer chemotherapy. MATERIALS AND METHODS: We examined thymidine kinase (TK) levels in 30 patients with colorectal cancer who underwent adjuvant or palliative chemotherapy (CHT schemes). The condition for being included in the study was a minimum of 3 cycles of chemotherapy. TK was always assessed with radio-receptor analysis, before and after every chemotherapy cycle, together with other tumor markers. RESULTS: From the monitored tumor markers, only TK changed typically in the course of chemotherapy. In adjuvant chemotherapy, it was mostly low at the beginning of the cycle and its values usually increased considerably at the end. On the other hand, in palliative chemotherapy the dynamics of TK varied mainly depending on the effect of the therapy. Other tumor markers showed nonstandard behavior and minimal correlation with TK changes. CONCLUSION: Thymidine kinase seems to be a suitable parameter for monitoring the effect of adjuvant and palliative chemotherapy in colorectal cancer.

Chemotherapy, Adjuvant↗