Relationship of carbohydrate antigen 19-9 and Lewis antigens in pancreatic cancer

Carbohydrate antigen (CA) 19-9 identified by a murine monoclonal antibody against a colorectal carcinoma antigen is thought to be a sialylated Lewis (Le)a blood group antigen and occurs in high concentration in serum of patients with pancreatic carcinoma. This study was designed to identify the relationship between Lewis antigens and CA 19-9 in patients with pancreatic cancer. The following analyses were performed in 20 pancreatic cancer patients: Lea and Leb antigen phenotype in saliva (modified enzyme-linked immunosorbent assay) or on red cells (hemagglutination); CA 19-9 levels (radioimmunoassay) in serum; and CA 19-9 and Lea and Leb expression (immunoperoxidase assay) on tumor tissue. Lea-b- patients based on salivary phenotype failed to express CA 19-9 in tumor tissue and had normal or low levels of CA 19-9 (less than 37 units/ml) in serum (P = 0.0011, versus Lea+b- and Lea-b+ patients). Eighty-eight % of Lea+b- and Lea-b+ patients had elevated serum CA 19-9 levels (greater than 37 units/ml). All Lea+b- and Lea-b+ patients expressed both Lea and Leb antigens in tumor tissue. These results support the view that Lea-b- pancreatic cancer patients cannot manufacture CA 19-9. Surprisingly, Lea-positive patients express Leb antigen in tumor tissue; in this subgroup, Leb antigen may be a tumor-specific biomarker.     

Elevated serum levels of Dupan-2 in pancreatic cancer patients negative for Lewis blood group phenotype

CA19-9, a serum marker for pancreatic cancer, gives false-negative results in patients who are negative for the Lewis blood group phenotype. To determine whether other markers may compensate for this drawback, serum levels of CA50, Span-1, sialyl SSEA-1 and Dupan-2 were assayed and compared with those of CA19-9 in 207 normal subjects and in 200 patients with pancreatic carcinoma whose Lewis blood group phenotypes were confirmed. In normal subjects with the Lewis negative phenotype, the serum levels of CA50 and Span-1, as well as CA19-9, were significantly low, whereas those of sialyl SSEA-1 were independent of the Lewis blood group phenotype. Serum levels of Dupan-2 were significantly higher in normal subjects with the Le (a-b-) phenotype as compared with those with Le(a-b+). The sensitivity for pancreatic carcinoma was 81% for CA19-9, 84% for CA50, 82% for Span-1, 51% for sialyl SSEA-1 and 63% for Dupan-2. Among the 39 CA19-9 negative patients, 13 were determined as being Lewis negative by the serum dot-ELISA technique. Although the positive rates were essentially comparable when each marker was combined with CA19-9, a highly elevated serum level of Dupan-2, which strongly suggested the presence of malignancy, was most frequently encountered in 39 patients who were not diagnosed by CA19-9 assay, especially those with Lewis negative blood groups. With regard to the three other markers, we found few patients with a highly elevated serum level in either the Lewis-negative or -positive groups. We conclude that Dupan-2 tended to be elevated in patients with pancreatic cancer who were negative for the Lewis blood group phenotype.     

Tumor markers--personal experience. The use of tumor markers for cancer of digestive organs]

This review is concerned mainly with our experience in the use of tumor markers for cancer of digestive organs from study of tumor markers by the author over the past 20 years. Development of a radioimmunoassay for highly sensitive detection of alpha-fetoprotein (AFP) by Ishii et al. in 1971 enhanced the usefulness of screening for early hepatocellular carcinoma (HCC) occurring in the course of liver cirrhosis. PIVKA-II, reported as a highly specific tumor marker for HCC, was thought to be less available for detection of early HCC occurring in the course of liver cirrhosis in comparison with AFP. Carcinoembryonic antigen (CEA), a most popular and useful tumor marker for cancer of digestive organs, was frequently positive in sera of colorectal cancer patients who had no subjective complaint or physical sign. This experience supported employment of CEA as a routine screening test for colorectal cancer. A survey of routine examinations of serum CA 19-9 for a period of one month in the clinical laboratory of our hospital proved that 92% of the positive cases of low-level CA 19-9 from 37 U/ml to 75 U/ml were noncancerous. This result indicated that the cut-off value of 37 U/ml employed for serum CA 19-9, which had been evaluated as a specific and highly sensitive tumor marker for pancreatic cancer and bile duct cancer, was too low. Accordingly, it was thought necessary to investigate a change of cut off value and reevaluate CA 19-9 for pancreatic cancer and bile duct cancer in comparison with other tumor markers of carbohydrate antigen such as CA 50, sialyl SSEA-1. From our experience in the use of tumor markers, the combination assays of fetal protein such as AFP, CEA, basic fetoprotein (BFP) and carbohydrate antigen, such as CA 19-9 and CA 50, for routine examination of tumor marker, are recommended for effective screening of cancer of digestive organs.     

糖抗原CA19—9测定对消化系统恶性肿瘤的诊断意义

Serum carbohydrate antigen CA 19-9 level was measured by radioimmunoassay in 55 patients with malignant digestive disease (14 esophageal cancers, 11 gastric cancers, 5 colorectal cancers, 14 primary liver cancers and 11 pancreatic cancers). The mean value of serum CA 19-9 levels was 22.11 +/- 24.79 u/ml in esophageal cancer, 99.91 +/- 100.12 u/ml in gastric cancer, 64.5 +/- 53.43 u/ml in colorectal carcinoma, 47.81 +/- 68.62 u/ml in primary hepatic cancer and 459.55 +/- 696.76 u/ml in pancreatic cancer (CA 19-9 greater than 37 mu/ml as positive). There were significant differences (P less than 0.05) between the mean serum CA 19-9 levels of pancreatic cancer and esophageal cancer, primary hepatic cancer. An increased CA 19-9 synthesis and excretion by tumor cells or increased pressure on pancreatic duct by the tumor may cause the elevation of serum CA 19-9 level in cancer patients. The authors conclude that CA19-9 is a valuable tumor marker in the diagnosis of pancreatic cancer and, probably, other gastrointestinal tumors.     

Clinical investigation of carbohydrate antigen CA-50

The CA-50 enzyme immunoassay kit (EIA kit) that has been developed with the use of C-50 monoclonal antibody prepared by L. Lindholm et al. was evaluated for diagnosis of human cancer. The levels of CA-50 in the sera were determined using this kit supplied from Mitsui Pharmaceuticals, Inc. Co. in 759 healthy donors, 728 patients with benign disease and 1,263 untreated patients with cancer. A CA-50 concentration of 40 U/ml of serum was used as the cut-off value. Patients with pancreatic cancer and patients with bile duct cancer had high positive incidence of 75% and 68%, respectively, compared with a low positive incidence of under 40% in patients with other cancers. On the other hand, positive rates in patients with benign disease were as low as 13%. Comparison of the serum levels of CA-50 with CA19-9 in the same samples did not exhibit complete positive correlation in patients with pancreatic cancer, patients with bile duct cancer and patients with liver cancer. These findings indicated that C-50 antibody reacted with two epitopes of CA19-9 and sialosyllactotetraose. From the above results, the usefulness of CA-50 as a tumor marker for pancreatic cancer and bile duct cancer was recognized with this EIA kit.     

Concentration and localization of carbohydrate antigen 19-9 in tissues of pancreatic cancer

Carbohydrate antigen (CA) 19-9 concentration in the tissue-extracts of cancerous and noncancerous pancreatic tissues were determined by radioimmunoassay. Pancreatic cancer tissues revealed significantly elevated CA 19-9 concentrations, when compared with chronic pancreatitis, normal adult pancreas, or fetal pancreas tissues. Metastatic liver tumors from pancreatic cancer also showed extremely high CA 19-9 concentrations, and there was no significant correlation between tissue CA 19-9 concentration and serum CA 19-9 level in patients with pancreatic cancer. In addition, positive localization of CA 19-9 was clearly observed in cancer cells of pancreatic cancerous tissues by immunohistochemical study, confirming the remarkable increase of CA 19-9 concentration in tissues of pancreatic cancer, although CA 19-9 was also partially found in non-malignant pancreatic tissues. The results indicated that CA 19-9 would be produced in great quantities by cancer cells in tissues of pancreatic cancer, and thus could be a valuable tumor associated antigen suggesting its clinical use as a tumor marker for cancer of the pancreas.     

Comparison of Serum Assays for TAG-72, CA19-9 and CEA in Gastrointestinal Carcinoma Patients

Tumor-associated glycoprotein (TAG-72) has been shown to beexpressed in a wide variety of epithelial malignant tissues.We have investigated serum levles of TAG-72 antigen in patientswith gastrointestinal cancer with a solid phase radioimmunometricassay (RIA), CA72-4, utiliz ing murine monoclonal antibodiesCC49 and B72.3 which recognize the TAG-72 antigen. Elevatedlevels of serum TAG-72 antigen were found in 48% of 56 gastriccarcinoma patients and 67% of 45 colorectal carcinoma patients.The serum concentrations of TAG-72 were compared to those ofCA19-9 and CEA. The positive rates of CA19-9 in gastric carcinomaand colorectal carcinoma patients were 29% and 54%, and thoseof CEA were 52% and 60%, respectively. Elevated serum levelsof TAG-72, CA19-9 and CEA were observed in 7%, 14% and 24%,respectively, of patients with benign disease, thus indicatinga preferential expression of TAG-72, compared to CA19-9 andCEA, in gastrointestinal carcinoma patients versus in patientswith benign disorder. A cocktail of CA72-4, CA19-9 and CEA RIAsincreased positive rates to 68% in sera of gastric cancer patientsand 84% in sera of colorectal cancer patients. Combination assays using CA72-4, CEA and CA19-9 RIM for patients with benigngastrointestinal disorder, however, also increased the positiverate to 31%. These results indicate that CA72-4, CA19-9 andCEA RIA may be complementary in detecting circulating tumor-associatedantigens. It must be emphasized, however, that interpretationof the data provided by the combination serum as says requirescareful consideration.     

Carbohydrate antigen 19-9 in tissues and sera from patients with gastric cancer

Detection of carbohydrate antigen (CA) 19-9 in tissues and sera was performed by an immunoperoxidase assay and by radioimmunoassay of samples from patients with gastric cancer. Twenty-eight of 102 (27.5%) gastrectomized patients and 13 of 21 (44.8%) patients with recurrent cancer showed abnormal and elevated levels of CA 19-9 in sera of more than 37 U/ml. Sixty-five of 102 (63.7%) patients gave positive localizations of CA 19-9 in cancerous tissues and 20 of 102 (19.6%) gave positive localizations of CA 19-9 in noncancerous gastric mucosa. Twenty-five of 28 (89.3%) patients with elevated serum CA 19-9 showed positive evidence of CA 19-9 in cancerous tissues, and 37 of 74 (50.0%) patients with normal serum levels of CA 19-9 also showed positive evidence of CA 19-9 in cancerous tissues. However, there were no clear relationships between CA 19-9 in cancerous tissues or in sera and the stage or histological type of the gastric cancer. These data indicate that CA 19-9 may be not released easily into blood circulation or that the concentration of CA 19-9 in tissues may be low, even though a large proportion of gastric cancer cells produces CA 19-9. It appears, therefore, that CA 19-9 will be restricted clinical use as a detector, monitor or tumor-associated antigen of gastric cancer.     

血清胆汁CA19-9、CEA、CA242联合检测诊断胆道良恶性肿瘤的可行性分析

目的:探讨血清、胆汁CA19-9、CEA、CA242联合诊断胆道良恶性肿瘤的临床价值。方法:对象为2013年10月-2015年2月来我院诊治的疑似恶性胆道肿瘤的患者202例,均行手术探查。所有患者均通过穿刺的方式取胆汁进行CA19-9、CEA、CA242检测,比较不同疾病类型患者血清、胆汁中的CA19-9、CEA、CA242检测水平,分析血清胆汁联合检测在胆道良恶性肿瘤中的诊断价值。结果:202例手术探查患者中,98例经病理证实为恶性胆道肿瘤患者、22例为良性胆道肿瘤患者,82例为其他胆道疾病。恶性胆道肿瘤与良性胆道肿瘤患者胆汁中CA242、CA19-9和CEA的表达水平要显著性的高于在血清中的表达水平（P＜0.05）;恶性肿瘤组患者的胆汁中CA242、CA19-9和CEA检测水平均显著性高于良性肿瘤患者（P＜0.05);胆汁CA242、CA19-9和CEA联合诊断胆道恶性肿瘤的敏感率为33.66%,准确率为88.98%,特异性为91.16%,阳性率为35.24%。结论:利用胆汁中肿瘤标记物对胆道肿瘤的检测水平要高于血清中的水平,采用CA19-9、CEA、CA242的联合检测是诊断胆道肿瘤比较理想的组合。上述肿瘤标志物的组合能够提高胆道肿瘤良恶性的预判准确度,对于早期胆道良恶性肿瘤的发现、治疗具有十分重要的意义。     

Serum determination of CA 19-9 in patients with digestive cancers and its diagnostic evaluation

The precision of CA 19-9 RIA kit was evaluated by recovery, reproducibility and dilution test with very satisfactory results. The CA 19-9 value in sera from 52 healthy individuals and from 224 patients with gastric intestinal cancer and other benign disease, showed an increased positive rate in several cases of gastric intestinal cancer. For example, the positive rate in pancreatic cancer, bile duct cancer, colo-rectal cancer, gastric cancer, esophagus cancer, primary biliary cirrhosis diabetes mellitus, liver cirrhosis and chronic hepatitis was 60%, 75%, 55.6%, 45.6%, 20%, 28.6%, 22.7%, 13.7% and 1.7% respectively. By contrast, values from patients with acute hepatitis, fulminant hepatitis, fatty liver, gastric duodenal ulcer, pancreatitis, and primary liver cancer were within the normal range. In this study, CA 19-9 RIA were found to be significant as an adjunct in the management of patients with gastrointestinal cancer, especially pancreatic cancer, and bile duct cancer.     

Comparative study of CA242 and CA19-9 in chronic pancreatitis.

CA242 has been proved to be useful in the diagnosis of pancreatic cancer. The aim of the present study was to clarify the mechanisms contributing to the high specificity of CA242 as compared with CA19-9 resulting from scarce serum elevation of this antigen in patients with chronic pancreatitis by correlating serum levels and endoscopic retrograde choledocho-pancreatography (ERCP) findings and by immunohistochemical analysis. Serum CA19-9 levels were significantly elevated in patients with calcification and with main pancreatic duct (MPD) stenosis or obstruction. On the other hand, serum CA242 levels showed no significant elevation in patients with such factors. Even though such pathological conditions were considered to lead to the stagnation of pancreatic juice, serum CA242 levels seemed to be less affected than serum CA19-9 levels. Immunohistochemical studies of chronic pancreatitis tissues revealed that CA242 was expressed less frequently and less intensely than CA19-9, and the difference in expression was more prominent in the centroacinar cells and terminal ductules. From the results of the present study, it is conceivable that CA242 is less influenced by the stagnation of the pancreatic juice than CA19-9 because of the low levels of expression in ductal systems, which results in the release of this antigen into the circulation in lower amounts than that of CA19-9.     

Tumor markers carbohydrate antigens CA 19-9 and CA-50 and carcinoembryonic antigen in pancreatic cancer and benign diseases of the pancreatobiliary tract

Sera from patients with diseases in the pancreas, gallbladder, and bile duct were analyzed for the tumor markers CA 19-9, CA-50, and carcinoembryonic antigen. In particular CA 19-9 and CA-50 appear to be valuable in differentiating malignant from benign disease in these organs. Our sample of 72 patients with pancreatic cancer also indicates that CA 19-9 and CA-50 complement each other in 21% of the cases. They are also shown to be reliable for monitoring disease: following radical surgery for pancreatic cancer low levels of CA 19-9 and CA-50 were noted, while progressive rises of these tumor markers were related to disease progression.     

Serological test of carbohydrate antigen CA50 in patients with cancer of the digestive tract

In order to determine the clinical usefulness of carbohydrate antigen CA50 as a marker for cancers of the digestive tract, an attempt was carried out to measure the CA50 levels (normal level less than or equal to 18.1 U/ml) in sera of patients with various diseases of the digestive tract including pancreatic cancer. In patients with pancreatic cancer, the frequency of elevation of CA50 was 85.7% (6/35), which was the highest frequency of elevation, and a serum level of over 1,000 U/ml was observed in 6 (17.1%) of these 35 pancreatic cancer patients. Furthermore, patients with gall bladder carcinoma, hepatocellular carcinoma and gallstones showed relatively high frequencies of elevation. On the other hand, the maximum level of CA50 in serum was 41 U/ml in patients with benign pancreatic disease. Therefore, it was thought that CA50 was able to differentiate pancreatic cancer from benign pancreatic disease in patients with pancreatic disease with extremely high levels of CA50. The serum level of CA50 showed significant correlation with that of CA19-9. This study suggested that CA50 might be a potentially useful marker.     

Combined determination of serum CA 19-9 and tissue polypeptide antigen: why no improvement in pancreatic cancer diagnosis?

CA 19-9 and tissue polypeptide antigen (TPA) were determined in the sera of 28 control subjects, 29 patients with pancreatic cancer, 26 with chronic pancreatitis and 62 with benign and malignant extra pancreatic diseases in order to compare their usefulness in diagnosing pancreatic cancer, to verify whether the combined assessment of the two indices could improve the results given by a single parameter and to speculate on the role of liver dysfunction in increasing their serum levels. The sensitivity, specificity and accuracy of CA 19-9 and TPA in diagnosing pancreatic malignancy were: 76, 85 and 61% for CA 19-9 and 79, 52 and 32% for TPA. The receiver-operating characteristic curves showed that CA 19-9 and TPA similarly discriminate pancreatic cancer from controls and chronic pancreatitis, while CA 19-9 is more useful than TPA in differentiating pancreatic malignancy from benign and malignant extra pancreatic abdominal diseases. TPA did not seem to add further information as compared to CA 19-9 alone when both markers were combined. Liver dysfunction may contribute to increasing serum levels of both markers.     

Immunohistochemical localization of CA 19-9 and CEA in pancreatic carcinoma and associated diseases

The distribution of carbohydrate antigen 19-9 (CA 19-9), on pancreatic carcinomas and associated diseases correlated with carcinoembryonic antigen (CEA) localization is described. Immunohistochemical examinations were made on pancreatic specimens from 45 patients with pancreatic carcinoma. In normal pancreatic duct, the antigens were restricted to the luminal surface. In some hyperplastic epithelium, however, they were localized not only to the basolateral plasma membranes but also to the cytoplasm. In neoplastic glands, the antigens were distributed over the entire surface of the cells and in the surrounding stroma adjacent to the basal membranes of the malignant cells. The findings were compatible with previous observations of CEA and secretory component (SC) localization in gastric and colonic mucosa. In addition, the staining intensity of CA 19-9 in the routine formalin-fixed and paraffin-embedded sections was much superior to that of CEA. The relationship between CA 19-9 and other blood group antigens, such as Lewis a and Lewis b, also was discussed. Localizations of these antigens in pancreatic tissues are useful for the biologic analysis of abnormalities of the pancreatic duct epithelium, and may well facilitate pathologic diagnosis of pancreatic carcinoma.     

The detection of human pancreatic cancer-associated antigen in the serum of cancer patients

A radioimmunoassay (RIA) test for human pancreatic cancer-associated antigen (Span-1) was developed to evaluate the diagnosis of various gastrointestinal disorders. Serum Span-1 in normal subjects ranged from 5 to 275 U/ml, with a mean of 58.8 U/ml (+/- 58.7, standard deviation). All control subjects had levels of less than 400 U/ml. Study subjects, 93% with pancreatic cancer, 59% with hepatobiliary cancers, 23% with gastric cancers, and 13% with colonic cancers had serum Span-1 levels greater than 400 U/ml. Sensitivities of Span-1, CA 19-9, and Dupan-2 for pancreatic cancer were 94%, 85%, and 38% respectively. Span-1 in patients with Stage I pancreatic cancer showed a 50% positive rating but CA 19-9 and Dupan-2 showed only 0% and 25%. Although a positive rating of these three antibodies increased in advanced cases, Span-1 showed the highest positive rating. Span-1 reacted with colonic cancer tissues with Lewisa-b- phenotype. However, none of these tissues did not react against CA 19-9. From these results, Span-1 has a good predictive value for detecting pancreatic cancer compared with CA 19-9 and Dupan-2.     

肿瘤标记物CA19-9、CA242对胰腺癌转移和预后预测价值的分析

目的:探讨肿瘤标记物糖类抗原19-9(CA19-9)、糖类抗原242(CA242)对胰腺癌转移和预后的预测价值.方法:选取80例胰腺癌患者和20例健康人群的血清样本,测定血清中CA19-9、CA242水平.探讨两者与胰腺癌临床分期、分型、肿瘤大小、淋巴转移情况和预后的关系.结果:胰腺癌患者血清CA19-9、CA242水平显著高于健康人群(P＜0.01).胰腺癌患者中Ⅲ+ Ⅳ期患者血清CA19-9、CA242水平显著高于Ⅰ+Ⅱ期患者(P＜0.05),淋巴转移患者血清CA19-9、CA242水平显著高于无转移患者(P＜0.05),生存期小于8个月患者血清CA19-9、CA242水平显著高于大于8个月患者(P＜0.05).以CA19-9 37.0U/ml、CA242 20.0U/ml为阳性阈值,以CA19-9阳性且CA242阳性组的正确指数最高.结论:胰腺癌患者血清CA19-9、CA242水平对胰腺癌患者术前诊断和预后分析具有一定参考价值.     

A clinical evaluation of carbohydrate antigen 19-9 and carcinoembryonic antigen in patients with pancreatic carcinoma

We have studied serum carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) in 221 persons to assess their usefulness in the diagnosis of pancreatic carcinoma. Although serum CA 19-9 and CEA in all healthy controls were within normal limits, the positive ratings of serum CA 19-9 and CEA in all benign disease were 9.8% and 18.1%, respectively. Sensitivity of serum CA 19-9 for pancreatic carcinoma was 70.5%, which was higher than that found in healthy controls, benign disease, and other malignant disease except biliary carcinoma; but sensitivity of serum CEA levels (67.7%) was not different from that seen in malignant disease. Three of 34 patients (8.8%) with pancreatic carcinoma who had a above-normal levels of serum CA 19-9 but not serum CEA were resectable. Although there was no correlation between serum CA 19-9 and CEA, advanced stages of pancreatic, gastric, and colorectal carcinoma tend to show high serum CA 19-9 and CEA, but no statistical differences were observed in relation to the stages of these carcinomas. Comparative studies of serum CA 19-9 and CEA for sensitivity and the predictive value of true positive and negative results for detecting pancreatic, gastric, and colorectal carcinoma showed that serum CA 19-9 has significantly higher sensitivity and predictive value of true positive results for pancreatic carcinoma than for gastric and colorectal carcinoma (P less than 0.05). However, serum CEA measurements did not show any difference between these carcinomas, and the highest predictive value of a true negative result for excluding pancreatic carcinoma was also observed in serum CA 19-9. These results indicate that although the CA 19-9 assay is not specific for pancreatic carcinoma, it is more useful adjunct method for diagnosing pancreatic carcinoma, possibly in resectable stages.     

外周血内CA19-9、CA242、CEA检测对不同病理分期胰腺癌的临床诊断价值

目的:分析糖类抗原19-9、糖类抗原242、癌胚抗原(CEA)检测对不同病理分期胰腺癌的临床诊断价值。方法:选取我院2015年7月至2017年1月收治的106例胰腺癌患者,检测血清CA19-9、CA242、CEA表达水平,比较手术治疗前后及不同临床分期胰腺癌患者血清CA19-9、CA242、CEA差异,评价上述指标对胰腺癌临床诊断及判断分期的指导作用。结果:胰腺癌病理分期越高,其血清CA19-9、CA242、CEA水平升高越显著,差异有统计学意义（P＜0.05）。肿瘤直径≥5 cm者、肿瘤位于胰腺体/尾部者,其血清CA19-9、CA242、CEA均显著高于肿瘤直径＜5 cm者及肿瘤位于胰腺头部或全胰腺者,差异有统计学意义（P＜0.05）。 结论:血清CA19-9、CA242、CEA有助于胰腺癌的临床诊断及分期判断,具有较高的临床价值。     

The diagnostic value of the foetoacinar pancreatic (FAP) protein in cancer of the pancreas; a comparative study with CA19/9

The serum diagnostic value of the foeto-acinar pancreatic protein (FAP protein), an oncofoetal pancreatic antigen, was tested in 201 patients. Of these, 112 suffered from malignant disease (57 patients had pancreatic carcinoma and 55, extra-pancreatic malignancies) and 89 had benign disease (49 patients with hepato-pancreato-biliary disease and 40 with other benign disease). FAP protein was measured by a competitive radioimmunoassay. In this technique, the normal cut-off level was 10% inhibition. This was deducted from values in 32 normal sera. FAP protein levels superior to 10% inhibition were found in 86% of patients with pancreatic cancer, in 31% with non-pancreatic malignancy, in 69% with benign hepato-pancreato-biliary disease and in 20% with other benign diseases. Accordingly, sensitivity of FAP protein for pancreatic carcinoma was 86% and specificity, 66%. However, high FAP protein levels (greater than 30% inhibition) were almost exclusively seen in patients with pancreatic cancer. At this cut-off level, specificity increased to 95% but sensitivity decreased to 51%. Determination of the carbohydrate antigen CA19/9 was made in parallel by a commercially available assay. At the cut-off level of 37 u ml-1, CA19/9 in our serum panel had a sensitivity of 74% for pancreatic carcinoma and a specificity of 88%. In pancreatic cancer 55 out of 57 patients had elevated levels of either FAP protein or CA19/9 (sensitivity; 96%).