Pancreatic Oncofetal Antigen Research Articles

The prospective evaluation of tumour-associated antigens for the early diagnosis of pancreatic cancer.

An unselected series of 136 patients suspected of having a major intra-abdominal pathological condition had blood drawn and stored as serum. A definitive histological diagnosis was made in all cases, usually by laparotomy. The serum was analysed with coded samples for carcino-embryonic antigen, alpha-fetoprotein and pancreatic oncofetal antigen and all recorded levels above the upper limit of normal for that test were taken as a positive result. Results were analysed to give the predictive value of a positive test and a negative test for each antigen. A negative pancreatic oncofetal antigen test was found to be useful in excluding a diagnosis of pancreatic cancer.

A clinical evaluation of serological diagnosis for pancreatic cancer.

AIM:To assess the diagnostic values of tumor markers for pancreatic cancer.METHODS:Pancreatic cancer-associated antigen from colonic mucosa (PCAAc), pancreas-specific antigen (PaA), pancreatic oncofetal antigen (POA) and minimolecular pancreatic antigen (mPOA) were detected by double antibodies Sandwich ELISA; CA19-9,elastase 1 (E1), human pancreatic elastase 1 (HPE1) and carcinoembryonic antigen (CEA) by radioimmunoassay (RIA); general activities of ribo-nuclease (RNase) and its isoenzymes (RNase I and RNase I) by biochemistry and PAEG;glycylproline dipeptidyl aminopeptidase (GPDA) by biochemistry andalpha 1-antitrypsin (alpha1AT) by rocket immunoelectrophoresis (rocket-IE).RESULTS:The detection of serum POA,mPOA,PaA,PCAAc,CA19-9,RNase and RNase I was able to differentiate pancreatic cancer from the benign disorders and non-pancreatic malignancies with a sensitivity from 66.75% to 80.0% and a specificity from 88.5% to 96.69%. POA, mPOA, PCAAc, HPE1, E1 and GPDA were related to the pancreatic cancer at the head which demonstrated higher sensitivity from 63.64% to 85.71%. The detection of serum HPE1 was especially helpful for the diagnosis of pancreatic cancer with smaller diameters. The determination of 3 or 4 kinds of tumor markers simultaneously would increase the detection rate of pancreatic cancer, which will be an important procedure for the diagnosis of this malignancy.CONCLUSION:A single test of tumor markers is helpful to detect pancreatic cancer clinically,but the determination of 3 or 4 kinds of tumor markers simultaneously would significantly increase the detection rate of pancreatic cancer, which will be an important procedure for the diagnosis of this malignancy.

Response to exogenous cholecystokinin of six human gastrointestinal cancers xenografted in nude mice

Gastrointestinal hormones regulate growth of cancers as well as normal tissues. We investigated whether long-term cholecystokinin (CCK) administration might affect growth or metabolism of human tumors xenografted in nude mice. In each experiment, approximately 20 nude mice bearing subcutaneous xenografts of the particular cancer line being studied were used. Half received CCK and half received saline solution intraperitoneally twice daily for 14 days. Tumor volume and body weight were measured every 3 days. If the tumors produced marker substances, these were measured in nude mouse serum and also in the xenografts. Tumor growth was significantly retarded by CCK in two of the six cancers studied. In each case, DNA, RNA, and protein reflected tumor volumes. In one of these tumors (SLU 077), serum carcinoembryonic antigen (CEA) levels paralleled the tumor volumes. In another tumor (SLU 132), serum CEA levels and tumor immunolabeling for CEA and pancreatic oncofetal antigen increased in response to CCK administration, whereas tumor volumes did not. These findings suggest that exogenous highdose CCK altered the growth and metabolism in two of six human cancers studied.

An immunoenzymatic method for pancreatic oncofetal antigen automated in the Boehringer ES 600.

An immunoenzymatic method for pancreatic oncofetal antigen automated in the Boehringer ES 600.

Pancreatic oncofetal antigen and carcinoembryonic antigen in breast and colon carcinoma.

Pancreatic oncofetal antigen (POA) and carcinoembryonic antigen (CEA) were determined in plasma of 195 patients with breast cancer and 90 patients with colon carcinoma. Increased levels of POA and CEA were seen in 19.0 and 25.6% of patients with breast cancer, respectively. Some but not all patients showed an increase in both markers. The incidence of abnormal concentrations of POA and CEA increased with the progress of the disease. POA appears to be a useful marker in breast cancer, especially in patients who have normal CEA levels. On the other hand, colon carcinoma patients showed increased POA concentrations considerably less frequently than CEA levels.

膵癌胎児抗原(POA)の特性とその免疫組織学的研究

膵癌胎児抗原(POA)の特性とその免疫組織学的研究

Biochemical analysis of meconium in fetuses presumed to have cystic fibrosis

A series of proteins (albumin, transferrin, alpha 1-antitrypsin, alpha-fetoprotein and pancreatic oncofetal antigen) and enzymes (gamma-glutamyltranspeptidase, aminopeptidase M, alkaline phosphatase, alpha-glucosidase and protease) was measured in fetal meconium extracts. There were 19 fetuses thought to have cystic fibrosis (CF), 13 with neural tube defects, three with chromosome abnormalities and 19 normal controls, all with gestational ages between 18 and 21 weeks. With the exception of alpha-fetoprotein, all the proteins and enzymes were significantly elevated in the CF meconium extracts. The most definitive indicator of a CF fetus was the albumin concentration, where the mean level was five times that found in the control groups. However, five of 19 fetuses assumed to have CF had albumin in the normal range. In these cases the meconium protease levels were grossly elevated. Furthermore, in the same five fetuses meconium concentration of pancreatic oncofetal antigen, a protein synthesized in the fetal pancreas, was also greatly raised. We suggest that post-mortem examination of a fetus thought to have CF should include measurement of meconium albumin, protease and pancreatic oncofetal antigen.

Diagnostic Significance of Cancer Antigen 125, Pancreatic Oncofetal Antigen, and Carcinoembryonic Antigen in Malignant and Tuberculous Pleural Effusions

Pleural fluid levels of cancer antigen 125 (CA 125), pancreatic oncofetal antigen (POA), and carcinoembryonic antigen (CEA) were determined in 56 patients with malignant pleural effusion and in 35 patients with tuberculous effusion. Malignant effusions had significantly higher pleural fluid CA 125 and CEA levels than those of tuberculous origin (p less than 0.005). No significant difference in POA titers was found between the two kinds of effusion. Assays of CA 125 and CEA in pleural fluid may be useful in separating malignant from tuberculous effusions. Concurrent measurement of CA 125 and CEA proved superior to determination of CEA alone in discriminating between the two groups.

Elevated pancreatic oncofetal antigen levels measured by enzyme immunoassay in pure pancreatic juice of patients with pancreatic cancer.

Pancreatic oncofetal antigen (POA) was measured by enzyme immunoassay in pancreatic juice from patients with pancreatic cancer, chronic pancreatitis, or other diseases. POA levels in pancreatic cancer were significantly higher than in other disorders, and POA was seen by immunofluorescence to be in the cancerous tissues of pancreatic cancer. Assay of POA in the pancreatic juice may be more reliable than serum POA, and could contribute to the diagnosis of pancreatic cancer.

Immunoperoxidase detection of pancreatic oncofetal antigen in human tissues

Normal human adult tissues (from the pancreas, stomach, small intestine, colon and rectum), human fetal pancreas and various human tumor tissues were investigated for the expression of pancreatic oncofetal antigen (POA) by the peroxidase-antiperoxidase complex method. The antibody used in this study was raised by immunization of rabbit with POA purified from ascites of a patient with pancreatic cancer; it was the same as in our previous report on enzyme immunoassay for serum POA. POA was localized in the ductal cells of human fetal pancreas and ductal cell type pancreatic cancer tissue. It was hardly seen in acinar cells of human fetal or adult pancreas, or in acinar cell type pancreatic cancer tissue. Several cancer tissues other than the pancreas revealed positive POA-staining but less frequently. POA was also detected in small amounts in the small duct of normal adult pancreas. In other normal human tissues, POA was recognized in deep crypts of the small intestine and colon. These results indicate that POA is present abundantly in immature ductal cells of the pancreas such as in fetal pancreas and pancreatic cancer, and that high serum levels of POA seen in patients with pancreatic cancer and other malignant tumors may originate from these malignant tissues.

Enzyme immunoassay of pancreatic oncofetal antigen (POA) as a marker of pancreatic cancer.

For the quantitative measurement of pancreatic oncofetal antigen (POA), an enzyme immunoassay for POA has been developed, and is based on the sandwich method using antibody-coupled glass beads and enzyme (peroxidase)-labelled antibody. Serum POA concentrations were increased significantly in patients with pancreatic cancer, but not in those with chronic pancreatitis or other miscellaneous diseases, or in normal subjects. It is concluded that the enzyme immunoassay could be used for the assay of POA and our results show that the determination of serum POA would be useful in the diagnosis of pancreatic cancer.

Serologic markers in the diagnosis and management of pancreatic carcinoma.

AbstractThe low prevalence of pancreatic cancer remains an inherent obstacle to the development of effective screening tools in an asymptomatic population. However, these difficulties do not warrant nihilism. Development of effective serologic markers still offers the potential for improvement in our diagnostic capabilities. The accurate identification of patients with pancreatic cancer and the exclusion of disease in those with benign disorders remain important goals. While alpha‐fetoprotein (AFP), human chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA), and ribonuclease (RNase) can be largely dismissed as useful markers of pancreatic cancer, leukocyte adherence inhibition (LAI), pancreatic oncofetal antigen (POA), and galactosyltransferase isoenzyme II (GT‐II) continue to show promise. Each of these markers currently requires further technical improvements to permit more widescale evaluation. The further refinement of monoclonal antibody defined markers such as gastrointestinal cancer antigens (GICA) may provide even more useful markers in the future. The development of effective serologic markers may help identify patients with early disease, and provide an impetus to develop more effective therapeutic strategies. It remains to be seen whether improvements in diagnostic modalities can be translated into improvement in clinical outcome.

Clinical application of the enzyme immunoassay for pancreatic oncofetal antigen.

Pancreatic oncofetal antigen (POA) purified by us has been detected in sera of patients with carcinoma of the pancreas by the micro-Ouchterlony method. In an attempt to improve the sensitivity and clinical usefulness of the serum POA assay, we established an enzyme immunoassay for POA and reported the results with this method. In this study, we investigated serum POA levels in pancreatic cancer and other diseases. The tissue localization of this POA in the pancreas was also studied. For the establishment of the enzyme immunoassay, an anti-POA-F(ab')2 fragment prepared from absorbed antiserum was conjugated with beta-D-galactosidase. The solid-phase "sandwich" principle was used. The normal upper limit of the serum POA level was defined as 400 units/ml. Among 60 patients with pancreatic cancer, 44 had elevated levels (73.3%). Of 22 cases with chronic pancreatitis, 4 had elevated levels (18.2%). In malignant diseases other than pancreatic cancer, elevated levels of serum POA were seen in 17.6% to 48.5% of the patients, most of whom had only slightly elevated levels. These results indicate that enzyme immunoassay for POA is clinically useful for making a diagnosis of pancreatic cancer. Immunoperoxidase staining showed POA to be found at the apical surface of ductular cells in fetal pancreas, at the luminal surface of glandular structures in pancreatic cancer tissue, and also at the luminal surface of the small duct in normal pancreas. Thus it is suggested that a high level of serum POA in patients with pancreatic cancer is derived from pancreatic cancer tissue.

Serum pancreatic oncofetal antigen: Its clinical usefulness for screening pancreatic cancer in combination with tests for other tumor markers

Screening for pancreatic cancer was carried out by serum pancreatic oncofetal antigen (POA) tests in 440 out-patients with abdominal complaints, with concomitant assay of carcinoembryonic antigen, alpha-fetoprotein and ferritin. POA was positive in 13 patients, of whom 3 cases of pancreatic cancer, and 4 of other malignant diseases were diagnosed while the remaining 6 were non-malignant. Of these out-patients, 5 cases were finally diagnosed as having pancreatic cancer by further examinations. Of these 5 patients, POA was negative in 2, of whom one was positive for CEA and AFP. Accordingly, when POA test was applied concomitantly with the other 3 marker tests, the detection rate of pancreatic cancer was elevated to 4/5. Twenty-three patients were found to have malignant diseases and 20 of them were positive for at least one of the 4 markers tested. These results suggest that serum POA assay is useful for screening the pancreatic cancer, especially when the other tumor markers are assayed concomitantly.

Pancreatic oncofetal antigen in pancreatic juices. Partial chemical characterization and diagnostic application of a pancreatic cancer-associated antigen.

Antisera were raised in rabbits to an antigenic structure present in fetal pancreas tissue, pancreatic tumor tissue, and pancreatic juices and in sera obtained from pancreatic cancer patients. The first chemical data indicate that this pancreatic oncofetal antigen is distinct from CEA, NCA, and NCA2 and is not glycolipid in nature. Immunoelectrophoretic analyses demonstrate that pancreatic oncofetal antigen is a protein or a glycoprotein, which displays microheterogeneity. The apparent molecular weight of the basic unit of pancreatic oncofetal antigen is estimated to about 40 K. So far 234 pancreatic juices have been investigated for pancreatic oncofetal antigen. Pancreatic oncofetal antigen was detected within the pancreatic juices from 59 of 74 (80%) pancreatic carcinoma patients but could be traced in only 16%-26% of samples obtained from patients with other diseases.

A pancreatic oncofetal antigen: its partial purification and clinical application.

Studies on the purification, characterization and clinical application of pancreatic oncofetal antigen were reported. This antigen was purified from fetal pancreas, and migrated in the beta-region on electrophoresis. Its molecular weight was about 80 x 10(4) daltons on gel filtration with a Sephacryl S-300. This antigen is clearly different from other oncofetal antigens such as alfafetoprotein, carcinoembryonic antigen or ferritin. Clinically, this pancreatic oncofetal antigen was positive in sera of 68.4% of the patients with pancreatic cancer. However, elevated level of this antigen was also observed in the sera of some patients with biliary tract cancer, colon cancer or gastric cancer. The antigen was also found in pancreatic juice obtained from patients with pancreatic cancer in almost the same incidence as in their sera. It is suggested that a pancreatic oncofetal antigen assay of sera and pancreatic juice in combination with other oncofetal antigens is valuable for the diagnosis and monitoring the clinical course of pancreatic cancer.

Tumor markers of pancreatic carcinoma.

There is no well-defined specific tumor marker for carcinoma of the pancreas. Carcinoembryonic antigen (CEA) and alphafetal protein (AFP) are produced by some pancreatic cancer cells. A pancreatic oncofetal antigen (POA) cross-reacts with other malignant neoplasms and is not produced by all pancreatic carcinomas. An ammonium sulfate fraction (0-25%) from an aqueous extract of pancreatic carcinoma tissues contains an antigen cross-reacting with extracts of other pancreatic carcinomas and various carcinomas representing all three germinal layers. A heterologous antiserum to this antigen cross-reacts with sera from patients with pancreatic carcinomas in a dilution of 1:16,000. At lower dilutions this antiserum reacts with sera from patients with other carcinomas and with sera from some apparently healthy individuals.

Prospective evaluation of some candidate tumor markers in the diagnosis of pancreatic cancer.

As part of a prospective diagnostic protocol, patients suspected of having pancreatic cancer had systemic and portal venous blood samples assayed, in coded batches, for peptide hormones and enzymes thought to be of potential value as tumor markers. An average of 111 patients were tested for each candidate marker. Results were analyzed by dividing patients into three groups according to the definitive diagnoses. These were pancreatic cancer (32% of patients), other cancers (27%), and benign diseases (41%). Although elevated mean levels of fasting plasma glucose and serum alkaline phosphatase were found in the pancreatic cancer group, there were no significant differences in the mean levels of any of the candidate markers studied in the three groups. The diagnostic values of normal and elevated levels of each candidate marker studied have been calculated. None has proven to be as useful as the serum level of pancreatic oncofetal antigen, fasting plasma glucose, or serum alkaline phosphatase in the diagnosis or exclusion of pancreatic cancer.

Non-operative differentiation between pancreatic cancer and chronic pancreatitis: Mackie CR, Cooper MJ, Lewis MH, Moossa AR, Ann Surg 189:480, 1979

Eighty-five of 186 patients investigated for suspected pancreatic cancer had an unequivocal final diagnosis of either pancreatic cancer (58 patients) or chronic pancreatitis (27 patients). They had been studied prospectively using ultrasonography, computerized tomography, radionuclide scanning, endoscopic retrograde cholangiopancreatography (ERCP), selective celiac and superior mesenteric angiography, duodenal drainage studies, cytologic studies, serum carcinoembryonic antigen assay, and pancreatic oncofetal antigen assay, The results were compared to determine which test would most frequently and reliably differentiate between pancreatic cancer and pancreatitis in a patient believed to have one or other disease. Criteria for interpreting results, first for highest rate of correct diagnoses, and second for highest accuracy were derived. Applying these criteria, ultrasonography achieved the highest rate of correct diagnoses (97% of patients diagnosed with 84% accuracy). ERCP, duodenal drainage studies, and cytology were the most accurate tests ((86% accuracy each test) but, with this accuracy, ERCP most frequently gave a diagnosis (diagnosis rate: ERCP--70%, duodenal drainage--32%, cytology--35%). The results suggest that ultrasonography is the best noninvasive test, and that a combination of ERCP, pancreatic juice assay and cytology in a single procedure may prove to be the best discriminating investigation.

Ultrasonography and tumor-associated antigens. The concept of combining noninvasive tests in the screening for pancreatic cancer.

A total of 134 patients suspected of having pancreatic cancer were given preoperative ultrasonic examinations. A total of 54 cases had a final diagnosis of pancreatic cancer histologically confirmed. The diagnostic sensitivity and specificity of the ultrasonographies were 76% and 91% or 87% and 74%, depending on whether doubtful results were called abnormal or normal. "Doubtful" results were defined as those that stated that pancreatic cancer was "possible" or "could not be excluded." When these results were divided into abnormal and normal groups on the basis of the patients' preoperative serum carcinoembryonic antigen and pancreatic oncofetal antigen levels, the sensitivity and specificity of the combined tests may prove to be a more accurate means of screening patients for pancreatic cancer than ultrasonography alone.