Plasma Carcinoembryonic Antigen Levels Research Articles

CEA serum levels in non-neoplastic disease.

Several non-neoplastic conditions, i.e., acute and chronic inflammations, benign tumors, renal or hepatic insufficiency, are associated with elevated plasma levels of Carcinoembryonic Antigen (CEA). Usually, CEA elevation in these pathologies is less than 10 ng/ml. CEA values in non-malignant disease can be affected by many factors, which can be classified into five main categories: a) tissular, b) physiological, c) metabolic, d) circulating and e) methodological factors. Synthesis, expression and release are the most important tissular factors. Among the metabolic ones liver, biliary and renal functions play a primary role in the determination of CEA concentrations. In addition, other factors such as the presence of circulating CEA-like substances, autoantibodies and immunocomplexes or the characteristics of the assay method can influence the diagnostic value of the CEA test. All these factors must be carefully considered when the marker is used in clinical practice.

Regional biologic therapy. Hepatic arterial infusion of recombinant human tumor necrosis factor in patients with liver metastases

Twenty-two chemotherapy-resistant patients with liver metastases received 46 courses of recombinant human tumor necrosis factor (rhTNF) administered by 5-day continuous infusion through percutaneously inserted hepatic arterial catheters. The maximum tolerated daily dose of rhTNF was 150 micrograms/m2. This is six times the maximum tolerated daily dose of rhTNF that could be given systemically (intravenous) on the same schedule. The dose-limiting toxicity resulted in severe, although transient, hypophosphatemia (less than 1.0 mg/dl) associated with myocardial dysfunction. Objective tumor response (partial tumor response or greater) was observed in 2 of 14 patients (14%) with colorectal cancer and lasted as long as 3 months. Three additional minor responses occurred among these patients with colorectal cancer. Plasma carcinoembryonic antigen levels also decreased significantly (greater than 25%) in 7 of the 14 (50%) patients with colorectal cancer. Regional biologic therapy with rhTNF as a sole modality has definite antitumor activity in colorectal cancer metastatic to the liver and warrants additional study in previously untreated patients.

Differences in messenger RNA expression of carcinoembryonic antigen in surgical specimens of colorectal carcinoma.

Carcinoembryonic antigen (CEA) is the most widely used tumor marker for colorectal cancer. Plasma CEA levels have been variably associated with prognosis. Since plasma CEA level is multifactorial, CEA gene expression in tumors may provide one precise mechanism to evaluate its functional role. This study evaluated CEA expression at the messenger RNA (mRNA) level in 22 human colorectal carcinomas and their adjacent normal mucosae by Northern blot hybridization using a 32P-labeled CEA probe (a loop-domain specific cDNA, LV7). Both tumor and normal mucosa displayed three mRNA species of 4.0, 3.6, and 3.0 kb in length. The expression of 3.6-kb mRNA which encodes for CEA was dominant and it was correlated with another 4.0-kb CEA mRNA expression. The expression of 3.0-kb mRNA which encodes for nonspecific cross-reacting antigen was weak and not detectable in 8 of 22 colon tumors and 12 of 22 normal colon mucosae. In only one tumor, a 4.5-kb mRNA (which might encode for a new family member of CEA) was expressed. A two- to fourfold higher expression of CEA mRNA (3.6 kb) was observed in 11 of 22 colorectal tumors (2 of 9 proximal colon tumors and 9 of 14 rectosigmoid tumors) when compared with morphologically normal adjacent mucosae. Preoperative plasma CEA levels and Dukes' staging had no correlation with this CEA mRNA expression. CEA mRNA did not appear to correlate with metastasis because its expression in the primary colon cancers with metastases (Dukes' stage D tumor) was not always increased. These data also imply that factors other than mRNA expression in tumor might be important in regulating plasma CEA levels.

Leukocyte Alkaline Phosphatase and Carcinoembryonic Antigen in Metastatic Colorectal Cancer Patients

Peripheral blood leukocyte alkaline phosphatase scores and plasma carcinoembryonic antigen levels in 26 patients with metastatic colorectal cancer were compared to those in 30 healthy controls. Patients had metastases to the liver and abdomen. The mean leukocyte alkaline phosphatase score in the metastatic colorectal cancer patients was significantly higher than in the control group (246 +/- 65 vs, 52 +/- 26, p less than 0.001); and the mean carcinoembryonic antigen level in the patients was also significantly higher than in the controls (110 +/- 100 vs, 4.9 +/- 3 ng/ml, p less than 0.001). One hundred percent of the metastatic cancer patients had elevated LAP scores and 73% of these patients had elevated CEA levels. There was a difference between the mean CEA levels in the patients with liver metastases and those with abdominal metastases (162 +/- 135 vs, 39 +/- 53 ng/ml, p less than 0.04). The results suggest that although both markers were elevated in metastatic colorectal cancer, the LAP score seems to be more useful in detecting metastatic disease, since we found 11% false negatives with the CEA level and 0% false negatives with the LAP score.

Leukocyte Alkaline Phosphatase and Carcinoembryonic Antigen in Colorectal Cancer Patients

Leukocyte alkaline phosphatase (LAP) scores in peripheral blood, and plasma carcinoembryonic antigen (CEA) levels were determined in 122 colorectal cancer patients, and compared to 30 healthy persons, who served as controls. Both markers are gradually elevated according to the severity of tumor penetration. LAP scores in Dukes'C and D (157 +/- 79) were significantly higher than in Dukes'A, B1 and B2 (81 +/- 43), p less than 0.001. CEA levels were also higher in Dukes'C and D (50 +/- 95) than in patients with Dukes'A, B1 and B2 (25 +/- 54), p less than 0.07, but less significantly. The LAP score has at least the same reliability as the CEA values as a marker of stage in colorectal cancer patients.

Immunoreactive Gastrin-Releasing Peptide in Medullary Thyroid Carcinoma

We have previously shown that immunoassayable concentration of somatostatin (SRIH) was elevated in 70% of 34 consecutive medullary thyroid carcinoma (MTC) tissue samples. In the present study gastrin releasing peptide (GRP)-like immunoreactivity was measured in tissue extracts from these 34 MTC (25 inherited, 7 sporadic, 2 unclassified) and in 7 normal thyroid tissue. Plasma SRIH, calcitonin (CT) and carcinoembryonic antigen were assayed in all patients. Normal thyroid tissue contained less than 61 pmol GRP per g wet weight; in contrast GRP concentration was elevated (62-7800 pmol/g) in 32/34 tumor extracts. The distribution of tissue GRP values were similar in sporadic as well as in familial MTC. We found no significant correlation between tumor GRP concentration and plasma SRIH (r = -0.05), plasma CT (r = -0.24), or plasma carcinoembryonic antigen levels (r = -0.21). Tumor concentrations of immunoreactive GRP and SRIH were positively correlated when logarithmic transformation was used (P less than 0.01). Thus GRP, as well as SRIH, is a major product of tumoral C cells in human MTC when systematically evaluated in a large number of cases.

Níveis plasmáticos da alfa-fetoproteína e do antigénico carcino-embrionário em doentes com tumores malignos gastro-intestinais.

Levels of alpha-fetoprotein (AEP) and carcinoembryonic antigen (CEA) were determined in the plasma of 142 patients with malignant gastrointestinal tumours. AEP was raised in only four patients (2.8%); two patients with carcinoma of the stomach showed relatively elevated levels. Abnormal CEA levels were found in 82 patients (57.7%). The patients' age with positive CEA levels was a greater than that of the patients with normal levels (p less than 0.05). In patients with gastric tumours CEA positivity was correlated with clinico-pathological stage (pTNM) and with the resectability rate (p less than 0.05). In patients with carcinoma of colon and rectum a greater incidence of elevated plasma CEA levels, as well as higher levels, were found in patients with carcinoma of the left colon than in those with right colon tumours. Statistically significant differences were found between the positivity rate and Dukes' grading (p less than 0.05), as well as between CEA levels in Dukes' stages C and 'D' (p less than 0.005). It is concluded that AFP has a very limited clinical role in patients with malignant extra-hepatic gastrointestinal tumours and that CEA may have a clinical role in tumours of the digestive tract, other than carcinoma of colon and rectum.

Somatostatin in medullary thyroid cancer.In vitro andin vivo studies

The authors evaluated the presence of somatostatin (SRIF) in the plasma and in the tumor tissue of a total of 22 patients with medullary thyroid cancer (MTC) and studied the effect of exogenous SRIF administration on basal and pentagastrin (PG)-stimulated plasma calcitonin (CT) and carcinoembryonic antigen (CEA) levels. Mean plasma SRIF concentrations were significantly higher than those found in normal controls, with five of 15 patients having plasma SRIF levels above the mean + 2 SD of normal controls. High immunoreactive SRIF concentrations were found in the extract of three tumor tissues but not in one follicular thyroid cancer or in one toxic diffuse goiter. By immunoperoxidase staining seven of 11 (63.6%) primary MTC and five of 13 (38.5%) metastases expressed SRIF antigen in a low number of cells and with a weak degree of staining. As expected, CT was expressed in almost 100% of the cases with positivity in most of the cells and strong degree of staining. Patients with positive SRIF staining in the primary tumor had longer survival than SRIF negative patients. Infusion of synthetic SRIF (11 micrograms/minute/45 minutes) produced a significant reduction of plasma CT (but not CEA) levels in 12 of the 15 patients submitted to this test. Maximal percent decrease of plasma CT ranged from 10.8% to 72.7% of the basal value and was usually observed between 30 and 45 minutes from the beginning of the infusion. When infused together with the injection of PG, SRIF was able to significantly (P less than 0.05) inhibit the PG-induced CT release in five of six patients tested. These results demonstrate the following: SRIF is present in a few cells of many primary MTC and less frequently in their metastases; tentatively, the expression of SRIF antigen in the tumor seems to be associated with longer survival; increased SRIF concentrations are found in the plasma of some patients with metastatic involvement; and treatment with exogenous SRIF reduces the basal and PG-induced CT (but not CEA) release from the tumor.

Leukocyte alkaline phosphatase and carcinoembryonic antigen in breast cancer patients: clinical correlation with the markers.

Leukocyte alkaline phosphatase (LAP) scores in peripheral blood and plasma carcinoembryonic antigen (CEA) levels were determined in 208 breast cancer patients with nonmetastatic disease. Patients were followed until clinical manifestations of metastases appeared. Then the LAP score and CEA level were analyzed in relation to the clinical appearance of metastases. Of the 208 patients studied, 58 developed metastases during the follow-up period. The LAP scores and CEA levels of this group of patients were compared to a control group of 60 breast cancer patients who did not develop metastases. Of the two markers, LAP score seems to be considerably more useful in detecting metastatic disease.

Impact of radiolabeled antibody imaging on management of colon cancer

One hundred patients with known or suspected colorectal cancer were studied by radioimmunoconjugate scintigraphy prior to operation. Study subjects received murine monoclonal anticarcinoembryonic antigen labeled with indium 111 (Indacea). Sensitivity of imaging was 76 percent for primary tumors, 44 percent for hepatic metastases, 38 percent for extrahepatic abdominal metastases, and 78 percent for extraabdominal metastases. Seventeen of 46 patients (37 percent) with known or suspected hepatic metastases and no evidence of extrahepatic disease by conventional imaging methods had extrahepatic metastases at exploratory surgery. Nine of the 17 patients had disease accurately predicted by the Indacea scanning. The management of each of these nine patients was, or could have been, modified by the scan findings and unnecessary surgery eliminated. A number of patients without postoperative disease had an unexplained increase in plasma carcinoembryonic antigen level due to production of human antimouse antibody. The addition of excess mouse immunoglobulin to the plasma prior to assay blocked this artifactual increase.

Adenocarcinoma of the lung

The reaction patterns in 80 adenocarcinomas of the lung were examined with PAP-method using a monoclonal antibody against keratin and one against carcinoembryonic antigen (CEA) and a polyclonal antiserum against CEA. Almost all tumors showed a positive reaction to the antibodies which, however, varied quantitatively. Even though a reliable correlation of positive immunohistochemical reaction with the different light microscopical types was not possible according to WHO subtypes and degrees of differentiation, specific localization of the reaction within the tumor cells was seen with increasing differentiation. There was no correlation between the immunohistochemical reactions and 14 clinically measured plasma CEA levels. The plasma CEA level not only depends on CEA production by the tumor but also on other factors.

Elevated levels of secretory immunoglobulins A and M in serum of patients with large bowel carcinoma indicate liver metastasis.

Preoperative serum levels of secretory IgA (SIgA) and secretory IgM (SIgM) were quantified by an enzyme-linked immunosorbent assay in 100 patients with large bowel carcinoma. The values obtained were related to tumor characteristics such as Dukes' stage, differentiation, DNA ploidy pattern, expression of secretory component (SC), volume, and plasma level of carcinoembryonic antigen (CEA). Statistical comparison was made with matched controls. Only patients with Stage D tumors showed significantly increased serum levels of SIgA and SIgM (P less than 0.004). The combined diagnostic sensitivity of SIg and CEA in Stage D was 0.94. In patients with liver involvement, serum SIgA and SIgM were elevated in 67% and 53%, respectively. However, circulating SIg was neither correlated with tumor SC expression nor with any other studied variable. Thus, the raised serum SIg levels were apparently not caused by release of SC from the tumors but, instead, by hampered liver function due to hepatic metastasis.

Non-human primate (baboon) anti-carcinoembryonic antigen antibody infusion in patients with metastatic adenocarcinoma. A phase I study.

A total of 14 patients with advanced visceral carcinoma which produced carcinoembryonic antigen (CEA) were treated in a Phase I study with IV infusion of affinity purified baboon anti-CEA antibody (dosage range from 0.1 to 2 mg/kg body weight). In all 14 patients, the antibody infusion caused a decrease (26% to 97%) in the plasma level of CEA. The degree of decrease depended upon the patients initial CEA level and the amount of antibody given. In 12 of the 14 patients "free" circulating antibody was observed. The plasma half-life of the antibody ranged from 0.7 to 21 h and the duration of detectable free antibody ranged from 3 to 216 h postinfusion. No toxicity was observed for the dosage range of antibody tested. In 9 of the 14 patients a low titer anti-baboon antibody response occurred between 14 and 28 days postinfusion. No clinical regression of carcinoma was documented. In 7 of the 14 patients disease remained stable during the 28-day study period. By the end of the 28-day study period plasma CEA levels had returned to at least the preinfusion level in 11 of the 14 patients.

Immunohistochemical demonstration of carcinoembryonic antigen (CEA) on tissue sections from squamous cell head and neck cancer and plasma CEA levels of the patients

45 squamous cell head and neck cancers including 36 with carcinoma of the oral cavity and 9 with carcinoma of the maxillary sinus were examined immunohistochemically for the presence of CEA. 12 of 30 carcinomas of the oral cavity and 7 of the 9 carcinomas of the maxillary sinus had tumors containing CEA. This difference in the occurrence of CEA was statistically significant. The mean plasma CEA level of 36 patients with carcinoma of the oral cavity and 7 patients with carcinoma of the maxillary sinus was 1.95±1.72 ng/ml and 3.70±3.53 ng/ml, respectively. Significant elevation of plasma CEA levels was found only in the stage-IV group patients with carcinoma of the oral cavity as compared with the stage-I group patients. In the 3 patients having plasma CEA values exceeding 5 ng/ml at the time of pretherapy, plasma CEA levels were decreased to below 2.5 ng/ml with the cancer treatment followed by the complete remission. These findings indicate that plasma CEA as a tumor marker in squamous cell head and neck cancer is meaningful in a small proportion of the cancer patient population.

Serial plasma carcinoembryonic antigen measurement for monitoring patients with advanced lung cancer during chemotherapy.

The plasma carcinoembryonic antigen (CEA) levels in 243 patients with untreated advanced lung cancer were studied to assess their value for prognosis and for indicating the effectiveness of chemotherapy. Of patients with adenocarcinoma, small cell carcinoma, squamous cell carcinoma, and large cell carcinoma, 43%, 24%, 7%, and 13%, respectively, had elevated CEA levels of 20 ng/ml or greater before treatment. Pretreatment CEA levels were elevated to above 20 ng/ml for 38% of 163 patients with extensive disease and for 22% of 80 patients with limited disease (P less than 0.02). In patients with adenocarcinoma of the lung, the pretreatment CEA levels were not correlated with response to chemotherapy and patients' survival. Serial measurement of plasma CEA was a useful noninvasive technique for monitoring the response to chemotherapy in patients whose pretreatment levels were 20 ng/ml or higher. All of 18 patients with complete or partial responses and 5 of 6 patients with minor responses showed greater than 36% decrease in the CEA level compared with the pretreatment level. In all of nine patients with progressive disease, the CEA levels increased after chemotherapy. Therefore, an increase of greater than 36% beyond the baseline level was a useful guideline criterion for a significant change for determination of tumor response to chemotherapy, although 41% of 22 patients with stable disease exceeded the pretreatment level by 36% or more in either direction (mean percent change +/- standard deviation, -4.1% +/- 52.2%), and 4 of 9 patients with progressive disease did not have levels greater than 36% above the baseline levels.

Palliation of pelvic recurrence of colorectal cancer with intra-arterial 5-fluorouracil and mitomycin.

Twenty-one patients with inoperable colon cancer in the pelvis were treated with intra-arterial 5-fluorouracil (5-FU) and mitomycin C, given bilaterally into the internal iliac arteries. Seventeen of the 21 patients had failed previous radiation therapy and 15 had also failed systemic intravenous chemotherapy. Eighteen of the 21 patients received intra-arterial treatments because of pelvic pain. Effect of this treatment on the pain could be evaluated in 16 patients. A measurable decrease in pain medication occurred in 8 of 16, whereas a subjective feeling of pain relief was observed in 12 of 16 patients for a mean period of 3.5 months. However, objective tumor response was considered definite only if associated with a greater than 50% decline of an elevated plasma carcinoembryonic antigen level; this was observed in 5 of 11 patients (45%). Reduction in tumor mass as measured by imaging techniques was observed in two of ten patients in whom it was evaluable. Improvement in hydronephrosis was observed in five of seven evaluable patients. Hematuria was present in 12 patients and improved in 10 of those patients. The most significant side effect of chemotherapy was perineal and gluteal skin erythema, which was observed in 36% of the patients after the first course and in 24% during the second course. This frequently escalated to cutaneous vesiculation and desquamation. This side effect was prevented by concurrent administration of steroids. Pelvic arterial infusion of 5-FU and mitomycin C can offer temporary pain relief to patients who have failed other means of therapy. Objective antitumor effects may have also resulted but were much harder to assess in this group of patients.

Serum β- N-acetyl hexosaminidase (β-NAH) as a discriminant between malignant and benign extrahepatic biliary obstruction: Comparison with carcinoembryonic antigen (CEA)

Fifty-one patients (16 with malignant extrahepatic biliary obstruction, ten with benign extrahepatic biliary obstruction, eight with alcoholic liver disease, five with viral hepatitis and 12 with liver metastases) and 19 adult healthy controls were studied with determinations of β- N-acetyl hexosaminidase (a lysosomal enzyme which is cleared from the circulation by the Kupffer cells), carcinoembryonic antigen (CEA), serum bilirubin, alkaline-phosphatase and aspartate aminotransferase (AST). Both CEA and β-NAH were elevated in each disease group. Elevated β-NAH levels distinguished between benign and malignant extrahepatic biliary obstruction better than CEA levels. β-NAH levels for the malignant and the benign groups were 47.6 ± 14.7 U/l and 23.0 ± 4.7 U/l (mean ± S.D.) respectively. The groups differed significantly ( P < 0.001). Plasma CEA levels for both groups were 18.7 ± 38.9 and 7.2 ± 3.3 ng/ml (mean ± S.D.) respectively. β-NAH levels for the 19 normal controls were 15.8 ± 3.5 U/l (mean ± S.D.). β-NAH also was significantly elevated in patients with hepatic metastases (36.9 ± 20.1 U/l). In 25 cancer patients with metastases other than in the liver β-NAH levels (18.3 ± 5.2) were not significantly elevated over the control group. It has potential value as a marker for non-CEA-producing liver metastases.

CEA tissue staining in colorectal cancer patients. A way to improve the usefulness of serial serum CEA evaluation.

The evaluation of serial plasma carcinoembryonic antigen (CEA) levels is one of the most important parameter used to establish the prognosis of surgically cured colorectal cancer patients. Carcinoembryonic antigen is particularly useful in the identification of recurrences and metastasis. However, to improve the usefulness of this assay, it would be helpful to accurately determine, if possible, those patients whose cancers produce CEA. The evaluation of the presence of CEA in these cancer specimens by means of immunoperoxidase staining technique does seem to improve the sensitivity of the CEA test. Fifty-seven patients with colorectal cancer who underwent surgical treatment were studied. Tissue CEA evaluation was correlated with the plasma CEA levels, the pathologic stage and grade, and histologic type of the cancers. Results demonstrate that 66.6% of Dukes' B cancers, 78.9% of Dukes' C, and 77.7% of Dukes' D cancers stained positively for CEA by immunoperoxidase. Thirty of 57 patients with preoperative pathologic plasma CEA levels had positive tissue CEA, whereas 8/57 patients did not. Of patients with a well-differentiated cancer (G1), 81.4% had positive tissue CEA versus the 64% of G2 and 60% of G3 cancers. The authors conclude that the use of the immunoperoxidase stain to measure CEA in tissue, so that the CEA serum assay may be used in those patients known to produce CEA, results in a major increase in the sensitivity of the test.

Immunohistochemical study of carcinoembryonic antigen in patients with colorectal cancer. Correlation with plasma carcinoembryonic antigen levels.

Using peroxidase-antiperoxidase (PAP) method, carcinoembryonic antigen (CEA) was demonstrated in conventionally processed colorectal cancer tissues. A new immunohistochemical grading for colorectal cancers based on the mode of the localization was made in an attempt to clarify the factors responsible for elevation of plasma CEA levels in colorectal cancer patients. Most of the patients with well differentiated adenocarcinoma, in which CEA was densely distributed along the apical surface but only rarely present along the basolateral surfaces of the carcinoma cells, had very low levels of plasma CEA, whereas all patients showing CEA distribution in the stroma as well as over the entire surfaces of the cancer cells and their cytoplasm showed high plasma CEA levels. In addition, there was a good correlation between the grading and presence of the blood vessel and lymphatic invasions. Thus, the appearance of CEA in the surrounding stroma, due to abnormal distribution of CEA on the basolateral plasma membrane of cancer cells, may play a significant role in the elevation of plasma CEA levels in colorectal cancer patients.

Immunohistochemical localization of tumor markers in epithelial ovarian cancer

Immunohistochemical determinations of carcinoembryonic antigen, α-fetoprotein, human chorionic gonadotropin (hCG), and human placental lactogen (hPL) were performed on tissue sections from 137 epithelial ovarian cancers. Fewer than 25% of serous cystadenocarcinomas contained detectable amounts of any marker. Carcinoembryonic antigen was present in over 50% of tumors, and was noted most frequently in mucinous, endometrioid, and clear cell carcinomas. hPL was demonstrated in 30% of endometrioid carcinomas but was rarely present in other cell types. Both α-fetoprotein and hCG were noted in fewer than 10% of all major cell types of epithelial ovarian cancer. Forty-five patients had serial determinations of plasma levels of carcinoembryonic antigen at the time of regular follow-up visits. Serial plasma levels of carcinoembryonic antigen accurately predicted recurrence in nine of 16 patients whose tumors contained carcinoembryonic antigen, in contrast to two of 16 patients whose tumors were devoid of antigen.