Elevated Carcinoembryonic Antigen Values Research Articles

Evaluation Of The Carcinoembryonic Antigen Test In Patients With Resected Colon Cancer

Abstract Introduction/Objective To determine the effectiveness of carcinoembryonic antigen (CEA) in patient with known residual disease after resection of colonic cancer Methods Serial carcinoembryonic antigen (CEA) levels were measured in 43 patients following incomplete excision of colorectal cancer. Twenty-seven patients received chemotherapy. The patients reported in this study were amongst those participating in a randomized trial of chemotherapy following palliative resection of colorectal cancer. All patients had a resection of colorectal cancer leaving behind macroscopic quantities of tumour, though of a small total residual bulk. The residual sites of tumour were recorded as: (a) local - where there was local extension of the tumour; (b) nodal - where there were clinically involved nodes remaining, with histological confirmation of involved nodes in the resected specimen; (c) hepatic - where small hepatic metastases were noted, individually not greater than 2 cm in diameter and in total representing less than 10% of the liver bulk; (d) peritoneal - where peritoneal tumour seedlings remained, with histological confirmation of at least one of the seedlings. Results Of the 43 patients studied after operation and prior to chemotherapy, the mean log CEA was 1.19 and only 3 patients exceeded 1.48, despite the fact that all patients were known to have residual tumour. Similarly, the mean log CEA at 3 months for the total group remained at 1.26 but 6 patients now had abnormal values. Thereafter the mean values of the total group exceeded the upper limit of normality and increasing numbers of patients showed elevated CEA values. About one half of the patients had levels of CEA well within the normal range during the first postoperative year despite the evidence of residual disease documented at operation. Conclusion The most appropriate application for a marker such as CEA may be as an assessment of the effect of chemotherapy in patients who have a definite, but objectively unmeasurable, tumour load.

Carcinoembryonic antigen (CEA) measurement during follow-up for rectal carcinoma is useful even if normal levels exist before surgery. A retrospective study of CEA values in the TME trial

Background Carcinoembryonic antigen (CEA) as a marker in the follow-up after curative resection of colorectal carcinoma (CRC) is often omitted from follow-up despite guideline recommendations. One reason is the assumption that when a normal CEA value exists before curative resection of CRC, it will neither rise during follow-up. This study investigates this relationship. Method Data were derived from a study initiated to evaluate treatment regimes for rectal carcinoma (Dutch TME trial, n = 1861) from which 954 were eligible for analysis. Recurrent disease occurred in 272 of these patients (29.5%). The pre-operative CEA value was compared to CEA values during follow-up, using threshold values of 2.5 and 5.0 ng/ml. Results Normal pre-operative CEA values were present in 63% (CEA < 5.0) and 39% (CEA < 2.5) of patients with recurrent disease. Patients with a normal pre-operative CEA and recurrent disease had elevated CEA values during follow-up in 41% (CEA < 5.0), 50% (CEA < 2.5) and in 60% with both threshold values when the last measurement was done within 3 months before recurrent disease was diagnosed. Conclusion A normal pre-operative CEA is common in patients with rectal carcinoma. CEA does rise due to recurrent disease in at least 50% of patients with normal pre-operative values. Serial post-operative CEA testing cannot be discarded based on a normal pre-operative serum CEA.

Increased serum carcinoembryonic antigen level in patients undergoing colon neobladder replacement compared with ileal neobladder replacement

Objectives. To compare the serum and urinary carcinoembryonic antigen (CEA) levels for assessment of possible risk of malignant transformation in patients with orthotopic neobladder. Methods. The serum and urinary levels of CEA, nutritional status, and acid-base and electrolyte balances were studied in 87 patients after radical cystectomy (22 with ileal neobladder, 28 with colon neobladder, and 37 with ileal conduit). The results of these groups were compared. Results. The serum CEA level in patients with colon neobladder, ileal neobladder, and ileal conduit was 5.4 ± 3.0, 3.7 ± 1.6, and 3.1 ± 1.5 ng/mL, respectively. The serum CEA level in the colon neobladder group was significantly higher than the levels in the remaining two groups ( P <0.05); 16 patients (57%) with colon neobladder had elevated serum CEA values (ie, greater than 5 mg/mL). Elevated serum CEA was observed in only 5 (23%) and 3 (8%) patients with ileal neobladder or ileal conduit, respectively. The serum CEA value in these patients was associated with the urinary CEA value ( P <0.001), but not the other factors examined. Conclusions. These findings suggest that colon bladder replacement caused significantly increased serum CEA values compared with ileal neobladder or ileal conduit; however, the elevated serum CEA level correlated with the urinary CEA level, irrespective of other clinical factors. Therefore, the elevated serum CEA in the colon neobladder group may have been due to reabsorption of CEA in urine rather than to an association with malignant changes in the bowel segments used for neobladder creation.

The carcinoembryonic antigen and its prognostic impact on immunocytologically detected intraperitoneal colorectal cancer cells

Background: Carcinoembryonic antigen (CEA) has been suggested to promote colon cancer progression. In this study we analyzed the prognostic impact of CEA expression on intraperitoneally detected single colon cancer cells. Methods: Peritoneal lavage samples of 135 colorectal cancer patients were imunocytologically analyzed, including a staining of cellular CEA; serum CEA levels were measured; and 5-year survival rates were calculated according to immunocytological findings and CEA expression. Results: The worst survival rate of 20% was found in patients suffering from CEA-expressing intraperitoneal tumor cells ( P = 0.0006). The prognostic impact of an intraperitoneal tumor cell finding significantly increased when serum CEA levels were elevated: only 23% survived 5 years in contrast to a 85% 5-year survival rate of patients who neither had signs of dissemination nor showed elevated serum CEA values ( P = 0.0010). Conclusions: This study shows that the determination of CEA expression improves the prognostic impact of an intraperitoneal tumor cell finding.

Serum Carcinoembryonic Antigen and DNA Ploidy in Colorectal Carcinoma

We have analysed the relationship between carcinoembryonic antigen (CEA) and DNA ploidy prospectively in 130 colorectal carcinoma patients. CEA was elevated preoperatively significantly more often in patients with DNA-aneuploid tumours than in DNA-diploid or DNA-tetraploid tumours--that is, in 48% (36 of 75) of patients with aneuploid tumours, in 34% (14 of 41) of patients with diploid tumours, but only in 14% (2 of 14) of patients with tetraploid tumours (p less than 0.05). Aneuploid tumours had an elevated CEA level in 38% of stage A-B disease and in 61% of stage C-D disease. The elevated CEA values (greater than or equal to 5.0 micrograms/l) correlated with tumour stage in patients with aneuploid tumours but not in patients with diploid tumours. Whereas CEA is a suitable marker for aneuploid carcinomas, other more sensitive tumour markers should be sought for diploid and also for tetraploid tumours. If such markers are found, flow cytometry could provide the most important information in selecting individual follow-up programmes for colorectal cancer patients.

Initial results with a commercial luminescence enhanced enzyme immunoassay for the determination of carcinoembryonic antigen (CEA) in body fluids.

A commercially available luminescence enhanced enzyme immunoassay (Amerlite--Amersham International) for carcinoembryonic antigen (CEA) was compared with an established enzyme immunoassay (Monoclonal 1-step Assay--Abbott Laboratories). A reference range for healthy blood donors (n = 272) was established for both kits. The blood donors were not separated into smokers and non-smokers, but were excluded from the reference group if they showed abnormal aminotransferase or gamma-glutamyltranspeptidase serum values. Twenty eight donors were excluded in this way. The test group consisted of 130 known tumour patients, and included pre- and post-operative serum samples. Normal and elevated CEA values were present. All sera were negative for HBsAg, anti-HBsAg and anti-HIV as determined with commercial enzyme immunoassays used routinely in the blood bank. The luminescence enhanced immunoassay gave rise to a reference range (95% confidence limits) of less than 3.91 micrograms/l in comparison with the enzyme immunoassay, which had a reference range of less than 4.12 micrograms/l. The proportion of elevated values in the tumour patient group was 37/130 for the luminescence enhanced enzyme immunoassay and 28/130 for the enzyme immunoassay. The correlation of values from both methods in the blood donor group was good (r = 0.771, n = 272). The CEA levels found in the tumour patient group differed significantly when measured in both kits (Wilcoxon matched-pair signed rank test--c-alpha = -6.52, p less than 0.01, n = 130), the Amersham kit giving the higher results (median values--Abbott 2.35 micrograms/l, Amersham 2.50 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Sandwich enzyme immunoassay using three monoclonal antibodies against different epitopes of carcinoembryonic antigen (CEA)

Purified monoclonal antibodies (Mab) produced by 3 hybridomas and reacting with 3 different epitopes of carcinoembryonic antigen (CEA) were used in a solid phase enzyme immunoassay. Two Mabs were physically adsorbed to polystyrene balls and the third Mab was coupled to alkaline phosphatase using the bifunctional reagent N-succinimidyl-3-(2-pyridyldithio)-propionate. During a first incubation, CEA from heat-extracted serum samples was immunoadsorbed to the antibody coated balls. After washing of the balls, bound CEA was detected by a second incubation with the enzyme coupled Mab. The sensitivity of the assay was 0.6 ng per ml of serum. A total of 196 serum samples from patients with various types of carcinoma, with liver cirrhosis, or from healthy blood donors with or without smoking habits, were tested. The results obtained with the monoclonal enzyme immunoassay (M-EIA) were compared with those obtained with perchloric acid extracts of the same serum samples tested by an inhibition radioimmunoassay using conventional goat anti-CEA antiserum. There was an excellent correlation between the two assays. In particular, the new M-EIA gave good results for the detection of tumor recurrences in the follow-up of colon carcinoma patients. However, despite the use of exclusively monoclonal antibodies the new assay detected a similar percentage of slightly elevated CEA values as the conventional assay in patients with non-malignant disease, suggesting that the CEA associated with non-malignant diseases is immunologically identical to the CEA released by colon carcinoma.

Carcinoembryonic Antigen in the Diagnosis and Management of Colorectal Cancer Patients with Liver Metastasis

Thirty-four colorectal cancer patients with liver metastasis (synchronous 20 cases, recurrent 14 cases were examined), and the usefulness and limitations of the determination of carcinoembryonic antigen (CEA) values were investigated. Among 20 cases of synchronous liver metastasis, elevated CEA values were found in 70%. In eight of these cases, CEA values were determined serially before and after resection of the cancer. In cases with preoperative elevated CEA values, CEA increased with enlargement in postoperative liver metastasis, but in cases with preoperative normal CEA values, the postoperative CEA levels changed only a little in some, while they increased in others. Among 14 cases of liver recurrence, elevated CEA values were found in 92.9%. In six of these cases, CEA levels were measured before and after recurrence. CEA showed abnormal values three to 10 months (six months on the average) before the detection of liver recurrence. Furthermore, the increase was rapid. Serial measurement of CEA levels in colorectal cancer patients was useful in the observation of the course of liver metastatis, the judgment of therapeutic effect, and the detection of liver recurrence. However, CEA values can be normal in the presence of obvious liver metastasis, and it is important to know both their usefulness and limitations.

The use of preoperative plasma CEA levels for the Stratification of patients after curative resection of colorectal cancers.

One hundred forty-five patients with colorectal cancer were analyzed in order to correlate the preoperative plasma carcinoembryonic antigen (CEA) levels with the sites and times of disease recurrence. The median follow-up periods of these patients was 50 months (range 36-72 months). Twenty-one patients were found to have metastases at the time of their operation. None of the seven patients whose primary tumors were classified as Dukes/Kirklin A have had tumor recurrence. Seventeen per cent of the patients with Dukes/Kirklin B tumors have had tumor recurrences, and 63% of the patients with Dukes/Kirklin C colorectal primary tumors have had tumor recurrence. No correlation was found between preoperative CEA values and subsequent risk of tumor recurrence or times to recurrence among the patients with Dukes/Kirklin B colorectal primary cancers. In Dukes/Kirklin C patients, however, elevated preoperative CEA values predicted a higher risk of tumor recurrence. Ninety per cent of the patients (19/21) with preoperative CEA levels greater than 5.0 ng/ml have had relapses, with a median time of 17 months before disease recurrence. Only 39% (9/23) of the patients with Dukes/Kirklin C lesions and CEA levels less than 5 ng/ml have had relapses and there is insufficient follow-up data as yet to determine the median survival time. If those patients whose Dukes/Kirklin C primary tumors were poorly differentiated on histologic examination are excluded, the contrast between patients having CEA levels greater than 5.0 ng/ml and those having CEA levels less than 5 ng/ml is even more marked. Sixteen of the 18 remaining patients whose CEA levels were greater than 5.0 ng/ml prior to curative resection have had relapses as compared with only three of 15 patients whose preoperative CEA values were less than 5. We conclude, therefore, that CEA is an important factor in stratifying patients after curative resection of their Dukes/Kirklin C colorectal tumors.

Carcinoembryonic antigen and ferritin in patients with lung cancer before and during therapy.

Carcinoembryonic antigen (CEA) levels were determined in 114 patients with confirmed lung cancer at the time of diagnosis using the CEA Ire-Sorin radioimmunoassay. Elevated CEA values were found in 47%. Most of the patients with high CEA levels had clinically detectable metastases. Ferritin was detectable by the Laurell-electrophoresis in the serum of 58 out of 81 (72%) of the patients with confirmed lung cancer at the time of diagnosis. Ferritin levels were significantly higher in patients with metastases. Serial measurements of CEA and ferritin during radio- and chemotherapy showed that the assay may be useful to evaluate the effects of therapy. Because of some false negative results both CEA and ferritin determinations should be used only in context with other clinical and laboratory findings.

Carcinoembryonic antigen in breast cancer.

Carcinoembryonic antigen (CEA) levels were determined in 742 postoperative patients with breast cancer. Within this group the percentage of elevated (greater than or equal to 4.0 ng/ml) assays increased with UICC clinical stage and was 14.8% (12/81), 23.7% (27/114), 73.1% (190/260) and 20.0% (49/245) for stages I, II, III, IV and X (unstagable due to insufficient data) patients. We have now followed the above 482 stages I, II, III and X patients in whom CEA was performed less than or equal to 3 months after initial surgery at a time when there was no evidence of residual disease, for an average interval of 255 days from date of diagnosis. At present 16.2% (17/105) of patients with elevated CEA values compared to only 4.8% (18/377) of patients with normal values have developed recurrent disease (p less than .0005). There is an association of elevation of CEA postoperatively with different clinical stages of breast cancer. Elevated CEA levels postoperatively are associated with an increased risk of development of recurrent disease in breast cancer patients.

Radioimmunoassay of carcinoembryonic antigen and clinical significance of its level in plasma.

The level of carcinoembryonic antigen (CEA) in the plasma was measured in 258 patients, consisting of 198 patients with various cancers and 60 with various non-malignant diseases. As the normal control, the plasma CEA level was examined in 330 apparently healthy individuals and the value was 3.1 +/- 1.1 ng/ml on the average. If the level higher than 4.2 ng/ml could be assumed to be above the normal, 109 out of 198 (55%) patients with malignant diseases were considered to show abnormally elevated CEA values. Based on the above criterion, the CEA titer was abnormally elevated only in 11 out of 60 cases (18%) without cancers. Among cancerous patients, the ones with carcinomas of the digestive tract and the lung exhibited a positive titer of CEA higher than 10.1 ng/ml. When the relationship between the plasma CEA level and histological findings in patients with lung cancer was examined, cases with the adenocarcinoma had more elevated titers than those with any other types of lung cancer. It was also found, by the serial estimation of plasma CEA, that the titer dropped after a successful therapy but elevated again with the recurrence of cancer. Repeated estimation of Cea is thought to be valuable as an indicator for clinical phases of cancer patients.

Carcinoembryonic antigen in patients suffering from ulcerative proctocolitis.

Carcinoembryonic antigen (CEA) has been measured by radioimmunoassay in samples obtained from all patients suffering from ulcerative proctocolitis and seen within a four-month period. The characteristics of this group of patients have been compared with reported epidemiological studies in this disease, and have been found to have a similar sex ratio and age of onset, but a more limited disease. Among 59 patients, 11 were found to have elevated circulating CEA values. One of the 11 had a colonic carcinoma and another was pregnant. Excluding these two patients, an overall prevalence of elevated CEA levels of 17.5% was found. The prevelance in ulcerative proctitis was 7.1%, and in colitis was 19.9%. The patients in whom elelvated plasma CEA values were found were compared with the remaining patients in relation to factors known to be associated with an increased propensity for the development of colorectal carcinoma complicating ulcerative colitis. There was no difference in mean age of the patients at disease onset, nor was there any difference in disease duration, extent, and control. A significant correlation was found between elevated plasma CEA levels and the severity of the initial attack. One patient with premalignant changes in the rectal mucosa had consistently normal concentrations of plasma CEA. There was no significant correlation between elevated plasma CEA values and disease activity. The mean age of the two groups of patients was similar. No carcinoma has manifested in any patient during follow-up periods of at least 18 months.

CEA as a monitor of gastrointestinal malignancy.

Ninety-four patients with carcinoma of the colon have been followed with serial determinations of plasma CEA (carcinoembryonic antigen) levels over a 3-year period using the Hansen assay. Nine hundred twelve CEA determinations have been made in these patients. Plasma CEA levels rose in 90% of the instances of clinical progression documented in these patients. In 30% of patients, this rise indicated progression 6 months or more before it was detected by standard clinical methods. Unfortunately, a few patients never developed elevated CEA levels even though disease clearly progressed. False positive results have also been encountered, with significant elevations occurring in patients who have since remained without evidence of disease for several months. Our data indicate that at least two sequential elevated CEA values, the second being higher, must be a minimal criterion for consideration of possible progression of disease. Even with this standard, we have encountered false positive results in 10% of our patients, indicating recurrence or progression where none has occurred clinically. CEA measurement is of limited usefulness for 30 days after curative surgery, because the elevation of CEA levels due to the original amount of tumor present as well as due to surgery per se may persist for this length of time in a significant number of patients. On the other hand, CEA levels have responded to chemotherapy in close correlation with observed clinical course in those patients with metastatic disease treated in this series. Initial pretherapy CEA values have so far proved to be good prognostic indicators of disease course following complete resection. With an initial CEA value of less than 2.5 ng/ml of plasma, recurrent has been rare (1/20). If the pretreatment CEA was greater than 7.0 ng/ml, it has been the rule (7/9).

Proceedings: Carcinoembryonic antigen. Report of a screening study.

Originally described as a specific marker for colonic carcinomas, carcinoembryonic antigen (CEA) has recently been demonstrated in elevated titers in patients with a variety of non-neoplastic diseases, especially in patients with serious metabolic disorders and in patients with inflammatory bowel disease. We are reporting results of CEA screening in 576 patients undergoing barium enema examination. None were known to have cancer, previously diagnosed or recurrent. Of this group, 23 were discovered to have primary or recurrent colonic cancers. CEA-radioimmunoassays by the Zirconyl phosphate gel method of Hansen were positive (>2.5 ng/cc) in 18 and greater than 5 ng cc in 15. However, in 4 of 13 early stage colonic carcinomas, CEA values were normal. Of the remaining 553 patients, none had proven cancer. Ninety-eight (18%) of them had elevated CEA values, but only 18 of these were greater than 5 ng/cc. Forty-six of these CEA positive patients had acute inflammatory bowel disease, acute gastrointestinal disorders, collagen diseases, or serious chronic metabolic diseases. Repeat CEA sampling in a third of the “false” positive group produced normal results in most. To date only 1 of the 98 “false” positive group is known to have developed a diagnosable cancer within the year. Of the CEA negative group, none have reported development of cancer. Caution is advised against interpreting a single elevated CEA value as synonymous with colonic cancer, and against dismissing the possibility of early colonic cancer in the face of a normal CEA value.