Detection of carcinoembryonic-like antigen on melanoma cells by leucocyte-dependent-antibody assays.

CEA-like antigen has been detected on the surface of some melanoma cells using a rabbit antiserum raised against CEA antigen in 51Cr-release leucocyte-dependent cytotoxic-antibody (LDA) assays. The CEA antigen used for production of the antiserum was shown to be immunologically pure by immunoelectrophoresis procedures and reacted with a reference serum to CEA. The specificity of the CEA antiserum for CEA on the melanoma cells was further shown by removal of reactivity to melanoma cells after absorption on CEA affinity columns. LDA activity to CEA was also shown in a serum taken during pregnancy. No CEA LDA activity was found in several melanoma sera. These findings suggest that CEA may have biological significance in tumour rejection, and that CEA assays may be of value in monitoring disease activity in melanoma patients.     

Choriocarcinoma: expression of tumor- and trophoblast-associated antigens in patients with low chorionic gonadotropin excretion.

The circulating levels of four tumor- or trophoblast-associated antigens were measured by specific radioimmunoassays in 11 patients with gestational choriocarcinoma. The estimations were carried out at the time when the urinary gonadotropin (hCG) excretion was low or negligible. Gonadotropin, measured as the hCG beta-subunit, was detected in serum of three patients, one of whom also showed a slightly raised level of carcinoembryonic antigen (CEA). All patients had normal serum alpha-fetoprotein (AFP) levels and no trace of human placental lactogen could be demonstrated. Repeat estimation after treatment of patients with raised levels showed a disappearance or a marked decrease of the circulating hCG levels and a return to normal of the elevated serum CEA level. The results show that although CEA levels may occasionally be elevated new information can hardly be expected from markers other than hCG when one is monitoring response to treatment, but AFP may have potential significance in the distinction between pregnancy and a trophoblastic disease. The circulating levels of hCG are of vital importance in the monitoring of choriocarcinoma patients who appear to be in remission by the conventional analysis of urinary hCG excretion.     

Carcinoembryonic antigen screening: pros and cons.

The appropriate use of plasma carcinoembryonic antigen (CEA) levels in the management of patients with colorectal cancer has been debated over the last 30 years. It is clear from the very low sensitivity of this test in normal populations that there is no role for CEA assessment as a screening tool for colon cancer. Although in patients receiving chemotherapy for metastatic colon cancer, elevations of CEA generally indicate disease progression, while decreases are indicative of improvement, there is no convincing evidence that CEA monitoring significantly affects either survival or quality of life. The area of most interest for CEA monitoring has been the potential for its use after curative resection. The purpose of postoperative CEA monitoring would be to detect recurrence of cancer at an early, surgically curable stage. There is good evidence that routine CEA monitoring postresection of colon cancer detects metastatic disease on average 5 months before routine follow-up evaluation without CEA monitoring detects recurrence. Also, studies demonstrate that some patients with recurrent cancer detected by CEA monitoring may be cured by surgical resection of metastases. However, the overall cost-effectiveness of this approach is not clear, and convincing definition of the role of postoperative CEA monitoring awaits the results of large randomized clinical trials.     

Serum tumor markers in metastatic breast cancer and course of disease

The purpose of this study was to compare the diagnostic significance of serum tumor markers in metastatic breast cancer and to evaluate their usefulness in monitoring palliative treatment. One hundred sixty-two breast cancer patients with various disease involvement have been followed-up by serum beta-human chorionic gonadotrophin (beta-HCG), alkaline phosphatase (AP), phosphohexose isomerase (PHI), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) analysis for 6 to 29 months. In metastatic disease, rates of elevated tumor marker levels ranging between 44% and 91% were found except for beta-HCG (13%). The low rate of positive beta-HCG values did not suggest that routine estimation may be useful. For the other markers, differences in positive rates were seen when site of metastasis, tumor burden, tumor activity, and stage of disease were taken into account. CEA and TPA were shown to be more sensitive indicators for metastatic disease than AP and PHI. TPA was more sensitive but less specific than CEA; both provided almost identical discrimination. In monitoring palliative treatment, a close correlation was found between the clinical course and changes of CEA. AP and PHI frequently became elevated only in very advanced disease, their elevation supported the clinical evidence of progression.     

Plasma carcinoembryonic antigen in the diagnosis and management of patients with hepatocellular carcinoma

The value of serial carcinoembryonic antigen (CEA) measurements as a marker of disease progression or in monitoring treatment was investigated in patients with hepatocellular carcinoma. Of 40 patients, including 16 with normal serum alpha-fetoprotein (AFP) concentrations, 29 (72.5%) had abnormal plasma CEA at presentation. Although this was more common in patients with pre-existing cirrhosis, the mean and range of plasma CEA were similar in patients with and without pre-existing hepatic disease. There was no correlation between plasma CEA and any biochemical parameter of hepatic function, although plasma CEA concentrations were significantly lower in patients with well-differentiated tumors. CEA concentrations increased in 71% of patients who had no response to cytotoxic drugs, but CEA also increased in 62.5% of those patients who did respond. Plasma CEA concentrations were elevated in 62.5% of patients with normal and 79% of patients with raised serum AFP on admission to the hospital. There was no correlation between individual AFP and CEA concentrations. Although elevated plasma CEA levels may be of diagnostic value in patients with hepatocellular carcinoma in the absence of pre-existing hepatic disease, and in those with normal serum AFP, our findings indicate that it does not behave as a true tumor marker.     

Comparison of plasma prolactin and CEA in monitoring patients with adenocarcinoma of colon and rectum.

Plasma prolactin (PRL) and carcinoembryonic antigen (CEA) were measured by radioimmunoassay in 74 patients with adenocarcinoma of colon and rectum. The markers were correlated with disease stage, histological grade and progression/remission of disease. The circulating preoperative median PRL and CEA levels were significantly higher in colorectal cancer patients than in their respective controls. PRL was elevated in all Dukes stages and in all histological grades of the tumour whereas the rise in CEA was more pronounced in Dukes D. Out of 74 patients, 29% (21/74) developed recurrent disease and 31% (23/74) responded to the treatment. With regard to monitoring recurrence(s), the predictive value of PRL was 94% which was significantly greater than that of CEA which was only 62%. In patients who developed liver metastases PRL remained elevated whereas CEA showed more than 100-fold increase. Therefore, we feel that CEA is a better marker for monitoring patients who developed liver metastases. From our results, we suggest that PRL can be used as a better overall marker for detecting recurrence(s) in patients with colorectal adenocarcinoma.     

Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines

In recent years, numerous serum and cell/tissue-based markers have been described for colorectal cancer (CRC). The aim of this article was to provide guidelines for the routine clinical use of some of these markers. Lack of sensitivity and specificity preclude the use of any available serum markers such as carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4, tissue polypeptide antigen (TPA) or tissue polypeptide-specific antigen (TPS) for the early detection of CRC. However, preoperative measurement of CEA is desirable as this may give independent prognostic information, help with surgical management and provide a baseline level for subsequent determinations. For patients with stage 2 (Dukes' B) and 3 (Dukes' C) disease who may be candidates for liver resection, CEA levels should be measured every 2-3 months for at least 3 years after diagnosis. For monitoring treatment of advanced disease, CEA should also be tested every 2-3 months. Insufficient evidence is presently available to recommend the routine use of other serum markers for monitoring purposes. Similarly, the new cell and tissue-based markers (e.g, ras, P53) cannot yet be recommended for routine clinical use.     

Evidence for the elevation of serum carcinoembryonic antigen and tumor-associated glycoprotein-72 levels in patients administered interferons

Sera were collected from 111 patients diagnosed with adenocarcinoma or nonadenocarcinoma malignancies who received different schedules of interferon (IFN)-gamma or IFN-beta ser alone or in combination. Serum carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72) antigen levels were measured to determine whether interferon could enhance the tumor shedding and, thereby, the serum level of either tumor antigen. Less than 10% of the sera samples from patients diagnosed with nonadenocarcinoma malignancies (e.g., hairy cell leukemia, melanoma) had positive titers of TAG-72 or CEA, and interferon neither increased nor resulted in the appearance of either tumor antigen in those sera. In contrast, 59.2% and 75.4% of the patients with adenocarcinoma had positive serum levels of TAG-72 and CEA, respectively, prior to interferon. IFN-gamma and IFN-beta ser alone or in combination significantly increased serum TAG-72 or CEA in approximately 65% of those patients. The results suggest that interferon administration to patients with adenocarcinoma can result in increased serum levels of selected tumor-associated antigens used in the diagnosis of malignancy. These preliminary findings may be important in the development of new strategies to obtain more sensitive tumor antigen serum assays for the diagnosis and monitoring for disease progression of adenocarcinoma.     

Carcinoembryonic antigen and prognosis after radical surgery for lung cancer: immunocytochemical localization and serum levels.

Eighty-two per cent of tumour sections from 105 patients with lung cancer showed positive immunocytochemical localization of an anti-carcinoembryonic antigen (CEA) immunoglobulin free of antibody to normal cross-reacting antigen (NCA). The highest incidence was found in adenocarcinomas, and no association between staining and disease stage was found. There was a relationship between positive-staining tumours and preoperative and postoperative serum CEA levels of greater than or equal to 20 ng/ml, but the high incidence of CEA+, less than 20 ng/ml serum patients indicated that immunocytochemical localization was of little value in selecting patients for sequential serum monitoring. Staining for CEA was not prognostic but a preoperative serum CEA levels greater than or equal to 20 ng/ml was associated with a poor prognosis in patients undergoing radical surgery for lung cancer (P = 0.043). this prognostic effect of CEA was seen mainly in patients whose tumours showed the greatest immunocytochemical localization (P = 0.017) and in Stage III patients (P = 0.04).     

Transient CEA increase at start of oxaliplatin combination therapy for metastatic colorectal cancer

In general a rising carcinoembryonic antigen (CEA) level means tumor progression. We observed a transient increase in CEA level despite objective response among patients receiving chemotherapy for metastatic colorectal cancer. This surge phenomenon has not previously been described for patients with metastatic colorectal disease. CEA was measured every second week in 27 patients receiving oxaliplatin, 5-fluororuracil, and folinic acid as first-line therapy against metastatic colorectal cancer. Four patients (15%, 95% CI 5-31%) met the criteria for therapy-induced CEA surge. The time of reaching maximum CEA level varied from 13 to 56 days. Median rise in CEA from baseline was 263% (range 24-632%). An initial rise of CEA during chemotherapy in colorectal cancer patients may therefore not always indicate progression of disease but may be a transient CEA surge in patients responding to chemotherapy.     

The value of carcinoembryonic antigen in patients with carcinoma of the lung.

Carcinoembryonic antigen levels in 682 lung cancer patients have been studied in order to assess their value in the screening of high-risk populations, monitoring total surgical ablation and projecting the effectiveness of therapy. The initial values are shown to be related to the histology of the tumor and to the extent of the disease. All histologic types of lung cancer produce elevated CEA but adenocarcinoma characteristically produces higher values than small, large or squamous cell carcinomas. CEA has its most precise value in distinguishing at an early date cured patients subsequent to surgical resection from those patients who will eventually fail because of recurrent disease.     

Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer

CEA is a complex glycoprotein produced by 90% of colorectal cancers and contributes to the malignant characteristics of a tumor. It can be measured in serum quantitatively, and its level in plasma can be useful as a marker of disease. Because of its lack of sensitivity in the early stages of colorectal cancer, CEA measurement is an unsuitable modality for population screening. An elevated preoperative CEA is a poor prognostic sign and correlates with reduced overall survival after surgical resection of colorectal carcinoma. A failure of the CEA to return to normal levels after surgical resection is indicative of inadequate resection of occult systemic disease. Frequent monitoring of CEA postoperatively may allow identification of patients with metastatic disease for whom surgical resection or other localized therapy might be potentially beneficial. To identify this group, serial CEA measurement appears to be more effective than clinical evaluation or any other diagnostic modality, although its sensitivity for detecting recurrent disease is not as high for locoregional or pulmonary metastases as it is for liver metastases. Several studies have shown that a small percentage of patients followed postoperatively with CEA monitoring and who undergo CEA-directed salvage surgery for metastatic disease will be alive and disease-free 5 years after surgery. Furthermore, CEA levels after salvage surgery do appear to predict survival in patients undergoing resection of liver or pulmonary metastases. However, several authors argue that CEA surveillance is not cost-effective in terms of lives saved. In support of this argument, there is no clear difference in survival after resection of metastatic disease with curative intent between patients in whom the second-look surgery was performed on the basis of elevated CEA levels and those with other laboratory or imaging abnormalities. There is also no clear consensus on the frequency or duration of CEA monitoring, although the ASCO guidelines currently recommend every 2-3 months for at least 2 years after diagnosis. In the follow-up of patients undergoing palliative therapy, the CEA level correlates well with response, and CEA is indicative of not only response but may also identify patients with stable disease for whom there is also a demonstrated benefit in survival and symptom relief with combination chemotherapy. More recently, scintigraphic imaging after administration of radiolabeled antibodies afforded an important radionuclide technique that adds clinically significant information in assessing the extent and location of disease in patients with colorectal cancer above and beyond or complementary to conventional imaging modalities. Immunotherapy based on CEA is a rapidly advancing area of clinical research demonstrating antibody and T-cell responses.     

Alpha-foetoprotein and carcinoembryonic antigen in germ cell neoplasms.

Serum alpha-foetoprotein (AFP) and serum carcinoembryonic antigen (CEA) levels were measured, serially whenever possible, in 70 patients attending the Institute of Radiotherapy, Rotterdam, on account of testicular (65) or ovarian (4) germ cell tumours or, in one case, an endodermal sinus (yolk sac) tumour in the mediastinum. In 15 patients the disease was active; in the others it was in remission. Patients with active disease had raised serum AFP levels which correlated well with disease activity; no patient without evidence of active disease had raised serum AFP levels. None of the patients with active disease was found to have raised serum CEA levels. There was no correlation between serum AFP and CEA levels in patients with germ cell neoplasms, but good correlation between serum AFP levels and disease activity. Serum CEA levels did not correlate with disease activity, and serial determinations would therefore not be useful in monitoring progress in this group of diseases.     

TPS in breast cancer--a comparative study with carcinoembryonic antigen and CA 15-3.

The serum levels of tissue polypeptide antigen were determined using the M3 monoclonal antibody (TPS) and compared with the serum levels of carcinoembryonic antigen (CEA) and breast carcinoma antigen 15-3 (CA 15-3) in 96 patients with benign breast tumors, in 25 breast cancer patients with no evidence of disease, in 139 preoperative breast cancer patients and in 298 samples of 25 breast cancer patients during therapy monitoring (4-22 samples per patient). The 95th percentile of TPS in 89 apparently healthy females was 51 U/l. The 95th percentile of TPS in patients with benign breast tumors was 55 U/l. The maximum TPS level in breast cancer patients with no evidence of disease was 56 U/l. In preoperative breast cancer the number of patients with TPS levels above the 95th percentile of TPS in benign breast tumors was significantly higher in stage III breast cancer as compared with stage I+II. This was not established for CEA and CA 15-3. During therapy monitoring TPS followed the course of the disease faster than CEA and CA 15-3 in patients with bone metastases, liver metastases, lung metastases and pleural effusion, with one exception. TPS levels could be correlated with progression of disease in patients with normal and steady levels of CEA and/or CA 15-3.     

Clinical Application of Serum Tumor Abnormal Protein (TAP) in Colorectal Cancer Patients

Objective: To explore the association of serum tumor abnormal protein (TAP) with other serologicalbiomarkers e.g. carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen19-9 (CA19-9) and its clinical application in colorectal cancer (CRC) patients. Methods: Patients (N=98) wereenrolled into this study with histologically or cytologically confirmed CRC. Using a test kit, the level of TAPwas determined, while chemiluminescence was used to measure the levels of some other common serologicalbiomarkers e.g. CEA, CA125 and CA19-9. Results: The area of TAP condensed particulate matter decreased afterchemotherapy compared with before chemotherapy when CT or MRI scans showed disease control. In contrast,it increased with disease progression (P<0.05). Furthermore, a statistically significant difference was confirmed inmonitoring of TAP and common serological biomarkers e.g. CEA and CA19-9 (p<0.05). Conclusions: DetectingTAP in CRC patients has high sensitivity and specificity and can be used as a new independent indicator forclinically monitoring CRC patients in the course of chemotherapy.     

Predictive value of serial carcinoembryonic antigen levels in long-term follow-up of ovarian cancer.

The predictive value of serial levels of carcinoembryonic antigen (CEA) in tumor monitoring was examined in 213 patients with ovarian cancer; each patient had been followed-up at monthly intervals for at least 12 months. CEA was not detectable throughout the period of observation in 35% of the patients. In general. patterns showing a disappearance of CEA or persistently low levels were associated with a good prognosis, whereas those showing a reappearance or highly elevated and rising levels were associated with a poor prognosis. A transient reappearance of CEA was observed in 10 patients; this did not appear to be associated with tumor recurrence or progression. "False positive" results were obtained in 6 patients in whom no tumor has been clinically detectable to date. "False negative" results were obtained in 4 patients with obvious tumor progression. In terms of a good or poor prognosis, the use of CEA levels was highly accurate in patients with minimal or no residual disease (97% and 89%, respectively); the rate fell to 62% in patients with extensive disease. As the clinical significance and limitations become better known, serial CEA levels should contribute substantially to the monitoring of patients with ovarian cancer.     

Carcinoembryonic antigen in patients with neuroblastoma

Carcinoembryonic antigen (CEA) was studied in the plasma of 17 patients (2 months to 18 years old) with neuroblastoma by means of a radioimmunoassay that detects an antigenic site in the CEA molecule at low ionic strengths. Elevated levels (greater than 2.5 nanograms per ml) of CEA were observed in plasma specimens from 8 or 9 patients with active neuroblastoma. Following successful therapy in 2 patients, CEA returned to normal in both. Disease remained active in 5 patients; their serial titers showed continued elevation. Seven of 8 patients with no evidence of active disease had CEA lèvels within the normal range. Ten children with nonneoplastic disease (2 to 10 years old) had normal levels of antigen (0-2.0 ng). This observation indicates that neuroblastoma may also possess the CEA previously detected in patients with other ectodermally derived cancers. The antigen appears to correlate with clinical activity of the neuroblastoma and may be helpful in assessment of the efficacy of therapy and prognosis in these patients.     

Tumor markers in lung cancer]

Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA), and pro-gastrin-releasing peptide (proGRP) can be used as tumor markers for lung cancer. CEA is sensitive for adenocarcinoma, SCC and CYFRA for squamous cell carcinoma, and NSE and proGRP for small cell carcinoma. A tumor marker is generally used as a marker to monitor the clinical course. Serum levels of pro-GRP, reflect the disease course of patients with small cell lung cancer more accurately than NSE or CEA. Among the patients with clinical N0-1 non-small cell lung cancer high serum CEA levels, adenocarcinoma histology, and large tumor dimension were significant predictors of pathologic N2 disease. CEA played a new role in predicting metastasis to mediastinal lymph nodes A more effective treatment may enhance the value of tumor markers to predict relapse.     

Diagnostic value of mucin-like carcinoma-associated antigen (MCA) in breast cancer

The diagnostic value of mucin-like carcinoma-associated antigen (MCA) was compared to that of carcinoembryonic antigen (CEA) and/or CA 15.3 in patients with breast cancer. A total of 368 patients with breast cancer were studied, of whom 253 were free of metastases, whereas 94 had either skeletal or visceral metastases or diffuse metastatic disease. The diagnostic sensitivity of MCA proved to be comparable to that of CA 15.3 and superior to that of CEA in patients with metastatic breast cancer. In contrast, the specificity of MCA was superior to that of CA 15.3. Finally, the diagnostic sensitivity of each of the tested tumour markers, i.e. MCA, CEA and CA 15.3, could be improved by their combined use. We conclude that MCA, either alone or in combination with CA 15.3 and CEA, can improve the monitoring of disease progression in patients with metastatic breast cancer.     

Evaluation of a new tumour marker in patients with non-small-cell lung cancer: Cyfra 21.1.

The Cyfra 21.1 assay is a newly developed test which measures in serum a fragment of cytokeratin 19. We evaluated this marker in 212 patients with non-small-cell lung cancer (NSCLC), predominantly stage 3a-b and 4, and compared it with three other markers: carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and tissue polypeptide antigen (TPA). Sensitivities for Cyfra 21.1, TPA, CEA and SCC (using cut-off levels corresponding to a 95% specificity for benign lung diseases) were 40%, 40%, 42% and 19% respectively. The sensitivity of CEA was significantly higher in patients with adenocarcinomas compared with the other three markers, while the sensitivity of Cyfra 21.1 and TPA was significantly higher in patients with squamous cell carcinomas. The value of Cyfra 21.1 for monitoring disease during chemotherapy could be evaluated in 23 patients with squamous cell carcinomas. When the cases of lead time were included a concordance between clinical evaluations according to WHO response criteria and evaluations according to changes in the marker levels of 74% was found. The criteria defined for marker response were a 65% decrease in the marker level for a partial response and a 40% increase for progressive disease. In particular, increasing levels of this marker indicated usually disease progression. In conclusion, Cyfra 21.1 is a useful serum marker for patients with NSCLC, especially for disease monitoring of patients with squamous cell carcinoma during and after chemotherapy.