Carcinoembryonic Antigen In Colorectal Cancer Research Articles

Optimizing the design and geometry of T cell engaging bispecific antibodies targeting CEA in colorectal cancer.

Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related deaths, with a 5-year survival rate of only 15%. T cell engaging bispecific antibodies (TCBs) represent a class of biopharmaceuticals that redirect cytotoxic T cells towards tumor cells, thereby turning immunologically "cold" tumors "hot." The carcinoembryonic antigen (CEA) is an attractive tumor-associated antigen (TAA) that is overexpressed in over 98% of CRC patients. In this study, we report the comparison of four different TCB formats employing the antibodies F4 (targeting human CEA) and 2C11 (targeting mouse CD3ε). These formats include both antibody fragment- and IgG-based constructs, with either one or two binding specificities of the respective antibodies. The 2+1 arrangement, using an anti-CEA single-chain diabody (scDbCEA) fused to an anti-CD3 single-chain variable fragment (scFvCD3), emerged as the most potent design, showing tumor killing at subnanomolar concentrations across three different CEA+ cell lines. The in vitro activity was three times greater in C57BL/6 mouse colon adenocarcinoma cells (MC38) expressing high levels of CEA compared to those expressing low levels, highlighting the impact of CEA antigen density in this assay. The optimal TCB candidate was tested in two different immunocompetent mouse models of colorectal cancer and showed tumor growth retardation. Ex vivo analysis of tumor infiltrates showed an increase in CD4+ and CD8+ T cells upon TCB treatment. This study suggests that bivalent tumor targeting, monovalent T cell targeting, and a short spatial separation are promising characteristics for CEA targeting TCBs.

The value of carcinoembryonic antigen stage in staging, prognosis, and management of colorectal cancer: results from two cohort studies.

Combining the carcinoembryonic antigen (CEA) level (C stage) with TNM staging can provide a more comprehensive prognostic assessment of colorectal cancer (CRC). However, the clinical value of incorporating CEA status into the TNM staging system needs to be evaluated. We used the SEER database (N = 49,350) and a retrospective cohort from China (N = 1,440). A normal CEA level was staged as C0 and an elevated CEA level was staged as C1. Restricted cubic spline analysis was used to examine the dose-response relationship between the CEA level and survival. The Kaplan-Meier method with the log-rank test was used to plot survival curves. Multivariable Cox proportional hazards regression models with forward stepwise variable selection were used to estimate the hazard ratios and 95% confidence intervals. Patients with C1 were more likely to have advanced disease than those with C0. CEA on a continuous scale was positively associated with mortality risk. Compared with patients with C0 stage, those with C1 stage had significantly lower survival rates. In the SEER dataset, C1 was independently associated with poor prognosis in patients with CRC, with an approximately 70% increased risk of mortality. Patients with C1 stage had significantly lower survival than those with C0 stage at all clinical stages. Incorporating the C stage into the TNM staging refined the prediction of prognosis of patients with CRC, with a gradual decline in prognosis from stage I C0 to stage IV C1. A similar pattern was observed in the present retrospective cohort study. At each lymph node stage, patients with C1 had significantly lower 5-year survival rates than patients with C0. Compared with lymph node positivity, CEA positivity may have a stronger correlation with a worse prognosis. Our findings not only validated the independent prognostic significance of CEA in CRC but also demonstrated its enhanced prognostic value when combined with TNM staging. Our study provides evidence supporting the inclusion of C stage in the TNM staging system.

Clinical implication of tissue carcinoembryonic antigen expression in association with serum carcinoembryonic antigen in colorectal cancer

This study aimed to evaluate the prognostic significance of carcinoembryonic antigen (CEA) expression in tumor tissues of patients with colorectal cancer (CRC). The cohort included 7,412 patients with CRC from January 2010 to December 2015. Survival outcomes were assessed based on tissue CEA (t-CEA) patterns and intensities. Three-year (76.7% versus 81.3%) and 5-year (71.7% versus 77.6%, p < 0.001) disease-free survival (DFS) rates were significantly (p < 0.001) poorer in patients with a diffuse-cytoplasmic pattern than an apicoluminal pattern. Three-year (79% versus 86.6%) and 5-year (74.6% versus 84.7%) DFS rates were also significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Three-year (84.6% versus 88.4%) and 5-year (77.3% versus 82.6%) overall survival (OS) rates were significantly (p < 0.001) poorer in patients with diffuse-cytoplasmic than apicoluminal pattern of CEA expression, and both 3-year (86.7% versus 91.2%) and 5-year (80.1% versus 87.7%) OS rates were significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Multivariate analyses showed that high-intensity t-CEA was independently associated with DFS (p = 0.02; hazard ratio [HR] = 1.233) and OS (p = 0.032; HR = 1.228). Therefore, high-intensity t-CEA is a significant prognostic factor in CRC, independent of serum CEA (s-CEA), and can complement s-CEA in predicting survival outcomes after CRC resection.

Predictive value of ABO blood type with Carcinoembryonic antigen in a Nigerians population with preoperative Colorectal Cancer

Abstract Introduction/Objective Earlier studies speculated possible link between ABO blood type and risk of malignancies. Given recent increase in Colorectal cancer (CRC) cases in Nigeria amidst poor facilities for early diagnosis, unraveling measures for prevention and prognosis become critical options. This study aims at assessing the predictive association of ABO blood types with preoperative Carcinoembryonic antigen (CEA) levels and some markers of gut immunostasis among southern Nigerian population with CRC. Methods The retrospective study evaluated 200 patients, scheduled for resection surgery for CRC between July, 2018 and September 2019 in Federal medical center Yenegoa, Nigeria. The relationship between the ABO blood types and CEA, interleukins, IL(6 and 8,) and Short chain fatty acids, SCFA (butyrate and propionate) were evaluated preoperatively using immunoturbidimetric assay, ELISA, and GC-MS respectively. The mean age of the patients was 51 years. The distribution of the ABO blood types in the patients were 60 (30.1%) for A, 50 (25%) for B, 79 (39.5%) for O, and 11 (5.5%) for AB. Patients with CEA levels &amp;lt;5 ng/mL, 6-30 ng/mL, and &amp;gt;30 ng/mL were classified as CEA Group 1, group 2 and group 3 respectively. Patient’s blood types, demographic characteristics and tumor locations, were recorded. SPSS, 22 was employed for data analysis. Results We determined a significant correlation between CEA levels and IL 6 in different blood types of CRC patients. No significant correlation was observed between CEA and gender. Blood type A showed significant increase in mean levels of CEA and IL 6 when compared to blood type B and O. No significant difference was observed in the mean SCFA levels among different blood types. Conclusion ABO blood type demonstrated significant prognostic value with CEA in colorectal cancer, with blood type A being most unfavorable.

Cutoff value of the preoperative serum carcinoembryonic antigen in the liver metastasis in colorectal cancer

Objective: To analyze the association between the elevation in preoperative serum carcinoembryonic antigen (CEA) levels and the incidence of liver metastasis in colorectal cancer (CRC) patients. In this study, the authors tried to determine the cutoff value of the preoperative serum CEA in the liver metastasis CRC. Methods: A total of 142 patients with histologically diagnosed CRC were obtained from patients’ medical records from 2015 to 2017, which met the research subject criteria. The variables were analyzed and included preoperative serum CEA in CRC patients with and without liver metastasis based on CT abdomen contrast at the time of initial diagnosis. Results: We found 41 patients (28.9%) with liver metastasis and 101 patients (71.1%) without metastasis. Serum CEA values (median and mean) in subjects with liver metastasis (28.7 and 28.9 ng/ml) were significantly higher than in subjects without metastasis (5.7 ng/ml and 7.1 ng/ml) (p 5 ng/ml significantly increases in the risk of liver metastasis. The calculation of the area under the curve (AUC) showed a value of 0.824 (82.4%) with a significant p-value (p < 0.001), and a cutoff CEA level of 12.0 ng/ml provides ideal diagnostic value (balanced sensitivity and specificity) to predict liver metastasis with the highest accuracy of 85.2%. Conclusion: The preoperative serum CEA levels were significantly increased in CRC with liver metastasis and can be used as a good biomarker to predict the presence of liver metastasis in CRC.

Abstract 4774: Engineering an oncolytic adenovirus to target CEA in colorectal cancer

Abstract Colorectal cancer is the second leading cause of cancer-related deaths in the United States and the third most commonly diagnosed cancer overall. Screening methods can identify precancerous polyps before they progress, leading to five-year survival rates of 92%. However, if diagnosed in later stages the survival rates decrease to 12%. While treatment options are available for advanced stages, they remain inadequate to affect overall survival. Thus, new therapies are needed to improve treatment outcomes. Oncolytic virotherapy is a unique therapeutic approach in which a virus is genetically modified to target cancer cells while sparing normal tissue. Oncolytic virotherapy takes advantage of the lytic properties of the viral life cycle. These viruses are used replicate inside cancer cells, lyse them and spread to adjacent cells throughout the tumor. The adenovirus is a well-characterized vector that is easily manipulated and produced and is capable of infecting a wide range of cells. However, the endogenous receptor for adenovirus, the Coxsackie and adenovirus receptor (CXADR), is often downregulated in cancers, thus decreasing the ability to selectively infect cancer cells. In this study, an adenovirus was genetically engineered to present the single variable domain (VHH) derived from a camelid heavy chain antibody B2. The B2 antibody recognizes the human carcinoembryonic antigen (CEA), which is often overexpressed in a variety of cancers, including colorectal cancer. Here, the wild-type fiber and knob domain of the adenovirus fiber gene was replaced with a modified T4 fibritin fiber linked to the B2 VHH. To provide for visual tracking of adenovirus infection and biodistribution, a red fluorescent protein (RFP) marker gene was also fused to the capsid protein IX (pIX). This virus was rescued and amplified in the HEK293 F28 packaging cell line with a final round of amplification in HEK293 cells. The virus was purified by CsCl ultracentrifugation and dialysis. The resulting viral stock was titered and characterized for the presence of the modified fiber and knob. Subsequently, the vector was modified to express the human sodium-iodide symporter (NIS) transgene, to allow for noninvasive imaging of the adenovirus uptake and replication as well as radiotherapy using 131I. Further experiments will be completed to confirm viral selectivity for CEA and subsequent lysis of colorectal cancer cells. The results of this study will advance targeting oncolytic adenoviruses to metastatic colorectal cancer. Note: This abstract was not presented at the meeting. Citation Format: Jessica C. Schaumburg. Engineering an oncolytic adenovirus to target CEA in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4774.

Effect of curcumin-containing chitosan nanoparticle on caspase-3, carcinoembryonic antigen in colorectal cancer induced by dimethylhydrazine

Background and aim Colon cancer is the third most common cancer for males and the fourth for females in Egypt. Previous studies have demonstrated that curcumin (CUR) is safely used against different cancers. This study was performed to evaluate the effect of curcumin-containing chitosan nanoparticles (CUR-CS-NP) against colon cancer induced by dimethylhydrazine (DMH) in rats. Material and methods The rats were randomly divided into four groups. The first group served as control group. The second group received DMH (20 mg/kg, subcutaneously) once a week. The third group was given DMH and CUR. Group 4 received DMH and CUR-CS-NP. The animals were sacrificed at the end of 10 weeks. Caspase-3 expression in colon tissues was determined by quantitative real-time PCR. Plasma levels of carcinoembryonic antigen (CEA) were determined by enzyme-linked immunoassay. Malondialdehyde (MDA), nitric oxide, and reduced glutathione were determined in plasma and colorectal tissues. Histopathological examinations of colon tissues were done. Results DMH treatment decreased caspase-3 expression, increased CEA, and oxidative stress levels. Pathologic lesions in the form of dysplasia and lymphocytic infiltration were seen in DMH-treated group. CUR-CS-NP and CUR treatments reduced the pathologic changes and increased caspase-3 expressions. Each treatment increased glutathione and reduced MDA, nitric oxide, and CEA levels. Conclusions Our study reveals that CUR and CUR-CS-NP have antioxidant and proapoptotic effects. So, it provides an insight towards the use of biological sources as promising anticancer agents.

Profile of carcinoembryonic antigen in colorectal cancer

Profile of carcinoembryonic antigen in colorectal cancer

Accessing new prognostic significance of preoperative carcinoembryonic antigen in colorectal cancer receiving tumor resection: More than positive and negative.

Evaluating the prognostic significance of carcinoembryonic antigen (CEA) for colorectal cancer (CRC) patients in new cutoffs. Three hundred and seventy cases and 1164 cases of CRC patients receiving tumor resection from hospitals of Sun Yat-sen University were retrospectively investigated as training cohort and validation cohort respectively. CEA was categorized into quintiles for Kaplan-Meier analysis and Cox proportional hazards regression analysis. CEA was categorized into quintiles with the cutoff points of (0-1.5) ng/ml, (1.5-2.3) ng/ml, (2.3-3.98) ng/ml, (3.98-8.02) ng/ml, (8.02-Maximum) ng/ml. In CRC patients from training cohort, progressively worse outcomes were observed in each increasing quintile of CEA in term of overall survival (Log-rank Test: P< 0.0001, Log-rank Test for Trend: P< 0.0001) and progression free survival (Log-rank Test: P= 0.0002, Log-rank Test for Trend: P< 0.0001). CEA quintile was associated with overall survival (HR: 1.209, 95%CI: 1.033-1.416, P= 0.018) and progression free survival (HR: 1.195, 95%CI: 1.024-1.394, P= 0.024). Validation analysis also showed that patients with increasing CEA quintile suffered unfavorable overall survival (Log-rank Test: P= 0.0001, Log-rank Test for Trend: P= 0.0001) and progression free survival (Log-rank Test: P= 0.0001, Log-rank Test for Trend: P= 0.0001). CEA quintile was associated with overall survival (HR: 1.330, 95%CI: 1.123-1.576, P< 0.001) and progression free survival (HR: 1.218, 95%CI: 1.089-1.362, P= 0.001). Preoperative CEA quintile was an independent predictor of unfavorable prognosis in CRC patients. Even within normal range, CEA quintile might still impact prognosis outcomes of CRC.

Expression of MCRS1 and MCRS2 and their correlation with serum carcinoembryonic antigen in colorectal cancer.

Cancer-associated genes serve a crucial role in carcinogenesis. The present study aimed to investigate the mRNA expression levels of microspherule protein 1 (MCRS1) and MCRS2 in colorectal cancer (CRC) and their association with clinical variables. The mRNA expression levels of MCRS1 and MCRS2 were assessed by semi-quantitative reverse transcription polymerase chain reaction in the tumor and corresponding non-tumor tissues of 54 newly-diagnosed CRC patients, as well as in the normal colonic mucosa tissue of 19 age/gender-matched healthy controls. Immunofluorescence was also employed to identify the expression of MCRS1 in CRC tissues, while the concentration of serum carcinoembryonic antigen (CEA) was determined by an enzyme-linked immunoassay. The results identified a negative correlation between MCRS1 and MCRS2 expression levels (r=−0.3018, P=0.0266). MCRS1 mRNA expression was significantly increased and MCRS2 mRNA expression was decreased in CRC tissues compared with the levels in the corresponding normal tissues (both P<0.001). An increase in MCRS1 expression and a decrease in MCRS2 expression was detected in advanced stage when compared with early stage CRC patients. Immunofluorescence analysis revealed increased expression of MCRS1 in CRC patients. Furthermore, the expression levels of MCRS1 displayed positive correlation, whilst those of MCRS2 displayed negative correlation, with the serum CEA level in patients with CRC. The results suggest that increased MCRS1 and decreased MCRS2 expression appeared to be involved in the pathogenesis of CRC. The present study provides evidence suggesting that MCRS1 and MCRS2 may identify CRC patients at a risk of disease relapse, and thus, may be potential tools for monitoring disease activity and act as novel diagnostic markers in the treatment of CRC.

A Higher Frequency of CD14+ CD169+ Monocytes/Macrophages in Patients with Colorectal Cancer.

ObjectiveMonocytes and macrophages can infiltrate into tumor microenvironment and regulate the progression of tumors. This study aimed at determining the frequency of different subsets of circulating monocytes and tumor infiltrating macrophages (TIMs) in patients with colorectal cancer (CRC).MethodsThe frequency of different subsets of circulating monocytes was characterized in 46 CRC patients and 22 healthy controls (HC) by flow cytometry. The frequency of different subsets of macrophages was analyzed in TIMs from 30 tumor tissues and in lamina propria mononuclear cells (LPMCs) from 12 non-tumor tissues. The concentrations of plasma cytokines and carcinoembryonic antigen (CEA) were determined. The potential association of these measures with the values of clinical parameters was analyzed.ResultsIn comparison with that in the HC, the percentages of circulating CD14+CD169+, CD14+CD169+CD163+ and CD14+CD169+CD206+ monocytes and TIMs CD14+CD169+ as well as IL-10+CD14+CD169+, but not IL-12+ CD14+CD169+ macrophages were significantly increased, accompanied by higher levels of plasma IL-10 in the CRC patients. The percentages of CD14+CD169+ circulating monocytes and TIM macrophages were associated with the stage of disease and correlated positively with the levels of plasma IL-10 and CEA in CRC patients.ConclusionOur data suggest that an increase in the frequency of CD14+CD169+ cells may be associated with the development and progression of CRC and is concomitant rise of both, pro-tumor (M2-like, IL-10 producing) and anti-tumor (M1-like, IL-12 producing) monocytes and infiltrating macrophages. The frequency of CD14+CD169+ circulating monocytes and infiltrating macrophages may serve as a biomarker for evaluating the pathogenic degrees of CRC.

Clinical Usefulness of Serum CYFRA 21-1 in Patients with Colorectal Cancer.

Among diverse tumor markers, pretreatment evaluation and follow-up detection of recurrence in colorectal cancer are generally evaluated by serum carcinoembryonic antigen (CEA) levels. However, there have been some reports about the low accuracy and high false-positive results of CEA in colorectal cancer. We investigated the clinical utilities of CYFRA 21-1 by comparing CEA and cancer antigen 19-9 (CA 19-9) in pretreatment and recurrent colorectal cancer. Using a solid-phase immunoradiometric assay, serum levels of CYFRA 21-1, CEA and CA 19-9 were analyzed in 132 patients with primary colorectal cancer, 124 healthy controls, 104 patients with benign colorectal disease and 19 patients with recurrent colorectal cancer. We determined three different cutoff values to evaluate the sensitivity of diagnostic performance in pretreatment and recurrent colorectal cancer. CYFRA 21-1 (≥ 1.13ng/ml) had a sensitivity of 47%, compared with 37% for CEA (≥ 3.05ng/ml) and 32.6% for CA 19-9 (≥ 23.1ng/ml) in the initial staging of primary colorectal cancer. Using different cutoff values, CYFRA 21-1 showed higher sensitivity for pretreatment colorectal cancer than CEA and CA 19-9 in adenocarcinoma and adenosquamous carcinoma of this study. A mildly significant correlative relationship was noted between Dukes' stages and three tumor markers (p < 0.01). The areas under the receiver operating characteristic curves of CYFRA 21-1, CEA and CA 19-9 were 0.81 ± 0.03, 0.74 ± 0.03 and 0.62 ± 0.04, respectively, for discriminating colorectal cancer patients from patients with benign colorectal disease. In addition, CYFRA 21-1 was determined as the most sensitive tumor marker for evaluating recurrent colorectal cancer for all cutoff values. This study showed that CYFRA 21-1 could be a useful and dependable tumor marker for pretreatment and recurrent colorectal cancer. Further prospective studies on its usefulness with respect to the prognosis and utility of combined tumor markers are needed.

The Evaluation of Diagnostic Value of the Tumor Markers: CCSA-2 and CEA in Colorectal Cancer

Finding the biomarker or biomarkers with high sensitivity and specificity in colorectal cancer, and thus a high diagnostic value will determine their clinical usefulness in clinical practice. An effective noninvasive blood test would be an ideal method to detect colorectal cancer. Discovered in 2007 a novel tumor marker CCSA-2 showes a promising results in patients with colorectal cancer. THE AIM OF THE STUDY was the evaluation of diagnostic and clinical value of a novel marker - colon cancer specific antigen-2 (CCSA-2) in colorectal adenocarcinoma in comparison to carcinoembryonic antigen (CEA) in patients operated during the years 2008 to 2010 at Wrocław Medical University 1st Department and Clinic of General, Gastroenterological and Endocrinologic Surgery. The study was performed on 40 patients with colorectal cancer and 40 patients in control group consisted of healthy subjects who had colonoscopy examinations with negative results (no pathology in the colon was found). The obtained results were statistically analyzed using nonparametric tests - Mann Whitney U and Kruskal-Wallis and Spearman's rank correlation coefficients. To determine the clinical value of CCSA-2 and CEA in those groups, their sensitivity and specifity was evaluated using ROC analysis. This analysis determines the accuracy and diagnostic value of both tests. There was a positive correlation between markers in patients with colorectal cancer and a statistically significant relationship according to which respondents with higher concentrations of CCSA-2 also have higher concentrations of CEA (R=0.754, p<0,001). Concentrations of tumor markers increase and correlate with the clinical progression of the disease. Accuracy of CCSA-2 test using ROC analysis showed a slightly lower measurement of antigen CCSA-2 as diagnostic value in colorectal cancer in comparison to measurement of antigen CEA (accuracy of tests: CCSA-2 - 52%, CEA - 60%). CCSA-2 as a single tumor marker has a low diagnostic value in colorectal cancer because of low sensitivity and specifity. The diagnostic value of novel marker is slightly lower than previously understood and accepted in clinical practice - CEA.

The relationship between heart rate variability and time-course of carcinoembryonic antigen in colorectal cancer

BackgroundIdentifying new prognostic factors is important for guiding treatments and preventing metastasis in cancer. Vagal nerve activity may predict prognosis in cancer due to its roles in modulating inflammation, sympathetic activity and oxidative stress. This study tested the relationship between heart rate variability (HRV), a vagal nerve index, and the colon cancer (CC) marker carcinoembryonic antigen (CEA), in an ‘historical prospective’ design. MethodsWe examined data of 72 CC patients, without inflammatory or cardiac diseases, of whom 38 had baseline electrocardiograms (ECG) and 12month CEA levels. We measured HRV (SDNN, RMSSD) from brief archived ECG. Multiple confounders were considered. ResultsControlling for effects of tumor stage and treatment-orientation, baseline HRV predicted CEA levels at 12months (r=−.43, p=.006). Patients with SDNN<20ms had significantly higher CEA at 12months than those with SDNN>20ms. ConclusionThese preliminary results showed that higher HRV predicts lower levels of a tumor marker, one year later, independent of confounders. This supports the hypothesized role of vagal activity in tumor modulation. Replication in larger samples is needed.

Estimating the Probability of Cancer with Several Tumor Markers in Patients with Colorectal Disease

Objective: The purpose of this study was to evaluate and compare serum tumor markers, carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4 and hCGβ, and their value in the diagnosis of malignant colorectal disease. Methods: The serum concentrations of the markers were measured in 204 patients with colorectal cancer and in 104 inpatients with benign colorectal disease. The combined use of the markers was evaluated with a logistic regression analysis. Results: When all five markers were evaluated in the same model, only CEA and CA 72-4 provided significant diagnostic information (p < 0.001), indicating that their combination improves the accuracy. The probability of cancer for each patient was calculated entering CEA and CA 72-4 in the logistic regression model. Receiver-operating characteristic curves were constructed, and the difference in the area under the curve (AUC) values was determined between the markers and the calculated probability of cancer. Of the individual markers, the highest AUC was observed for CEA (AUC = 0.746). The difference in the AUC between CEA and CA 72-4 (AUC = 0.716) was insignificant (p = 0.492), but between CEA and the other three markers it was significant (p < 0.015). The calculated probability of cancer index, based on a combination of CEA and CA 72-4, had a significantly higher AUC (AUC = 0.804) than CEA alone (AUC = 0.746; p = 0.046). Conclusions: The diagnostic value of CA 72-4 was additive to that of CEA in colorectal cancer, and both markers contributed with significant diagnostic information. As a diagnostic test, the probability of cancer calculated with logistic regression provided higher accuracy than any of the markers alone, implying that it might be a useful diagnostic tool.

Carcinoembryonic Antigen as a Marker for Colorectal Cancer: Is It Clinically Useful?

Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers worldwide. Its main application is mostly in gastrointestinal cancers, especially in colorectal malignancy. Although in use for almost 30 years, the clinical value of CEA in colorectal cancer is still not clear. The literature relevant to the clinical value of CEA in colorectal cancer was reviewed. Particular attention was paid to studies involving metaanalyses and guidelines issued by Expert Panels. Although of little use in detecting early colorectal cancer, high preoperative concentrations of CEA correlate with adverse prognosis. Serial CEA measurements can detect recurrent colorectal cancer with a sensitivity of approximately 80%, a specificity of approximately 70%, and can provide a lead time of approximately 5 months. CEA is the most frequent indicator of recurrence in asymptomatic patients and currently is the most cost-effective test for the preclinical detection of resectable disease. CEA is most useful for the early detection of liver metastasis in patients with diagnosed colorectal cancer. Overall, however, little evidence is available that monitoring of all patients with diagnosed colorectal cancer leads to enhanced patient outcome or quality of life. Currently, the most useful application of CEA is in the detection of liver metastasis from colorectal cancers. Because of the relative success of surgery in resecting hepatic metastases, serial determinations of the marker are recommended for detecting cancer spread to the liver. In the future, preoperative concentrations of CEA may be included with the standard staging procedures for assessing prognosis.

Monitoring Carcinoembryonic Antigen in Colorectal Cancer: Is it Still Useful?

Monitoring Carcinoembryonic Antigen in Colorectal Cancer: Is it Still Useful?

Monitoring carcinoembryonic antigen in colorectal cancer: is it still useful?

The results of a study conducted to determine the usefulness of carcinoembryonic antigen (CEA) monitoring in the follow-up of patients with resected colorectal cancer are reported herein. The subjects of this study were 125 patients in whom CEA had been determined preoperatively and 239 patients in whom CEA had been monitored postoperatively. The results revealed increased preoperative CEA in only 24% of the subjects, and that this increment was correlated with subsequent more advanced tumor stage and a higher recurrence rate (P < 0.01). The postoperative CEA level exceeded the threshold in 71% of the patients affected by recurrence, 94.4% of whom developed liver metastases and 50%, nonhepatic recurrence. This marker showed elevated sensitivity for liver metastases (99%), whereas the sensitivity was lower for nonhepatic recurrence of the disease (94%). Thus, we concluded that CEA monitoring can be useful for preoperative colorectal tumor grading, even if its validity in the early diagnosis of recurrence is problematic, especially in terms of radical repeated surgery and survival.

Within-subject variation of carcinoembryonic antigen in colorectal cancer -- application of reference of change values and individual reference ranges to patient follow-up.

Dynamic interpretation of results is an alternative approach to the conventional cut-off procedure. Reference change limit is a valuable reference point to interpret dynamically tumour marker values when only very few serial results can be obtained from a patient after treatment. In this paper, a reference change limit of 2.0 microg/l was estimated for carcinoembryonic antigen in patients with complete remission of colorectal cancer. This figure means that a difference greater than 2.0 microg/l has at least a chance of being statistically significant (at 0.05 probability). As complementary information to the reference change limits, with more than four successive results, a simple time series model can be used to obtain predictive limits for the next observation.

A prospective study of the use of 111In-labelled monoclonal antibody against carcino-embryonic antigen in colorectal cancer and of some biological factors affecting its uptake.

This prospective study of radioimmunoscintigraphy using 111In-labelled, C46, a monoclonal antibody against carcino embryonic antigen, CEA, was undertaken in 23 patients with colorectal cancer, 18 with primary carcinomas, 3 with recurrences and 2 with metastases. A sensitivity of 95% and an accuracy of 91% was found. New observations through the use of two administered doses of antibody and the analysis of surgical specimens showed that for the low dose of antibody (average 0.76 mg) tumour uptake was 1.14 x 10(-2)% of the injected dose per gram, whereas on the higher dose (average 4.67 mg) the average tumour uptake was 6.77% (same units) p less than 0.01. Thus a six-fold increase of antibody caused a six-fold increase in tumour uptake, but no change was seen in the tumour to mucosa ratio 4.8 +/- 0.5 (low dose) and 4.0 +/- 1.0 (high dose). A further observation was that well and moderately differentiated tumours took up about four times more than poorly differentiated tumours (p less than 0.05). It was also found that tumour free lymph nodes had a six-fold greater uptake than tumour involved nodes (p less than 0.05) confirming other work with anti-CEA monoclonal antibody. In conclusion, although biological factors influence its efficacy, 111In labelled C46 anti-CEA is a suitable radiopharmaceutical for the radioimmunoscintigraphy of colorectal cancer.