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.     

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.     

Tissue expression of the tumor marker CA 50 in benign and malignant pancreatic lesions. A comparison with CA 19-9

The expression of the tumor marker antigen CA 50, defined by the monoclonal antibody (MAb) C 50, was studied by the immunoperoxidase technique in formalin-fixed, paraffin-embedded tissue sections from normal pancreata, from pancreata with pancreatitis and from benign and malignant pancreatic neoplasms. The results were compared with those obtained with Mab 1116 NS 19-9. The C 50 antibody reacts, like the 1116 NS 19-9 antibody, with sialosylfucosyllactotetraose (corresponding to sialylated blood group antigen Lewisa), but also with another sugar moiety, sialosyllactotetraose. Thirty-two of 37 well- to moderately-differentiated adenocarcinomas and all cystadenocarcinomas were positive for CA 50. The staining was most intense in the apical border of the cells, and in the intraluminal mucus. The number of positive cells was smaller in poorly differentiated adenocarcinomas and only occasional cells were stained in anaplastic carcinomas. In acute and chronic pancreatitis small terminal ducts, centro-acinar cells and some large ducts stained for CA 50. In normal pancreas only a few small terminal ducts were CA-19-9-positive, whereas both ducts and centro-acinar cells were C-50-positive. Normal pancreatic tissue adjacent to carcinoma usually stained more strongly for CA 50 than the carcinoma, whereas the opposite was true for CA 19-9. Eight out of 11 CA-19-9-negative carcinomas were CA-50-positive. Serous cystadenomas and malignant islet-cell tumors were focally positive for CA 50, but negative for CA 19-9. It seems apparent that the C 50 antibody reacts with another determinant than sialylated Lewisa in CA-19-9-negative specimens, serous cystadenomas and malignant islet-cell tumors. Serum CA 50 and CA 19-9 levels were determined in 29 patients with pancreatic cancer. The sensitivity was similar for both markers (76%), and there was a positive correlation between the serum levels. However, there was no correlation between the serum levels and the histological expression of the CA 50 and CA 19-9 antigens.     

Study on the clinical usefulness of NCC-ST-439 in cases of digestive tract cancer

NCC-ST-439 is a monoclonal antibody established from human stomach cancer xenografted nude mice. The values of NCC-ST-439 were measured in 139 cases with various digestive tract cancers and 294 cases with benign digestive tract diseases with the NCC-ST-439 EIA kit (Nihon Kayaku Co., Ltd.), and its clinical usefulness was compared with those of CA19-9 and CEA. The positive rates of NCC-ST-439 in cases of digestive tract cancer were high, i.e., 66.7% for cancer of the bile duct, 58.3% for pancreatic cancer and 52.9% for colorectal cancer. In the benign digestive tract diseases, the overall positive rate seen in case of cholelithiasis and cholangitis, chronic gastritis, benign colorectal diseases and hepatitis, was only 3.7%. The positive rate of NCC-ST-439 was lower than those for CA19-9 and CEA in cases of stomach cancer, colorectal cancer and liver cancer, but it was the same as that of CA19-9 and higher than that of CEA in cases of biliary tract cancer and pancreatic cancer. The false positive rate of NCC-ST-439 in benign diseases of the digestive tract was the lowest among the three markers. With respect to sensitivity, specificity and efficiency, CA19-9 showed the highest sensitivity, but NCC-ST-439 and CEA showed better specificity than CA19-9, and NCC-ST-439 showed the highest efficiency. In combination assays using combinations of NCC-ST-439, CA19-9 and CEA, the positive rates for ST-439 alone were 22.1% for stomach cancer, 52.9% for colorectal cancer, 15.0% for liver cancer and 58.3% for pancreatic cancer, while the combined rates increased to 51.9%, 70.6%, 75.0% and 66.7%, respectively. In an investigation of changes with time in NCC-ST-439 values during chemotherapy of various types of digestive tract cancer, there was a decrease in PR cases, no change in NC cases and a tendency to increase in PD cases. These results suggested that it was possible to apply NCC-ST-439 clinically.     

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。     

CA 19-9 enzyme immunoassay

The carbohydrate antigenic determinant (CA 19-9) EIA kit (FUJIREVIO INC) was examined both experimentally and clinically. In the basic study, the standard curve showed linearity from to 240 U/ml, and the intra-and interassay reproducibility was good. Serum levels of CA 19-9 were determined by EIA in 246 cancer patients and 180 patients with benign diseases, and CA 19-9 levels by EIA were compared with those by RIA in concurrent measurement. There was an excellent correlation between the two. The positive of CA 19-9 EIA was almost the same as that of CA 19-9 RIA in cancer patients. False-positive cases by CA 19-9 EIA were somewhat more numerous than those by CA 19-9 RIA in patients with benign diseases, especially liver diseases. However, CA 19-9 assay by EIA is simple and has an excellent reproducibility and accuracy, as does that by RIA. Thus, the CA 19-9 EIA is a very useful assay.     

Cancer-associated tumour markers CA 19-9 and CA-50 in patients with pancreatic cancer with special reference to the Lewis blood cell status

Monoclonal antibodies 19-9 and C-50 were used to assay the cancer associated tumour antigens CA 19-9 and CA-50 in plasma from patients with confirmed pancreatic cancer, and related to the blood group and Lewis blood cell status. The plasma expressions of CA 19-9 or CA-50 were similar, including cases where the patients had Lewis phenotype Le (a-b-). However, analyses of both the tumour antigens could be used to differentiate the presence of cancer from its absence in Le (a-b-) individuals. The findings indicate that the targets for the monoclonal antibodies 19-9 and C-50 are similar. The practical implications of these findings are discussed.     

Serum CA 50 as a tumor marker in pancreatic cancer: a comparison with CA 19-9

CA 50 is a new tumor marker based on a monoclonal antibody (MAb) against a human colorectal carcinoma cell line. The CA 50 antigen is similar, but not identical, to the tumor marker CA 19-9. The serum concentrations of CA 50 were measured by an immunoradiometric assay (CA 50 IRMA) in 95 patients with pancreatic cancer and in 94 patients with benign pancreatic, biliary and hepatocellular diseases. The CA 50 concentration was above the cut-off limit of 17 U/ml in 71% of the patients with pancreatic cancer. Elevated CA 50 levels were also seen in 29% of the patients with benign diseases (up to 250 U/ml), especially in patients with extra-hepatic cholestasis (34%) and hepatocellular jaundice (46%). The results of the immunoradiometric assay were compared to those of the commercially available CA 50 RIA inhibition test. The sensitivities of the two CA 50 assays for pancreatic cancer were similar, but the specificity of the IRMA assay was higher. The CA 50 and CA 19-9 values showed a strong positive correlation and the assay parameters of the tests were almost similar. CA 50 seems a promising tumor marker in the detection and follow-up of patients with pancreatic cancer.     

Clinical evaluation on an enzyme immunoassay kit for basic fetoprotein (BFP). (2) Comparison and combination of BFP with other tumor markers

Comparison of basic fetoprotein (BFP) with 10 other tumor markers was made with sera from 549 patients with benign diseases and 870 patients with cancers, using BFP-EIA kit and commercial kits for others. BFP-positive rates higher than CEA or CA19-9 were found in various cancers except CEA in cancer of the colon, pancreas and lung, or CA19-9 in cancer of pancreas and bile duct. Furthermore, BFP showed higher positive rates in comparison with AFP in cancer of liver and testis, SLX(sialyl SSEA-1) or SCC in lung cancer and CA125 in uterine cancer. The correlation coefficient of BFP with other tumor markers except for SCC in lung cancer were low (below 0.262) in cancer and benign diseases. The combined assay of BFP with some other makers such as CEA in cancer of the digestive organ, lung, markers ovary and uterus, CA19-9 in cancer of the bile duct and lung, CA125 in ovarian cancer, AFP in cancer of the liver and testis, and PAP in prostatic cancer, showed an elevation of diagnostic efficiency compared with single assay. These results indicate that BFP is superior to other tumor markers for serological diagnosis of various cancer and also available for the combined assays.     

Immunocytological detection of micrometastatic cells: Comparative evaluation of findings in the peritoneal cavity and the bone marrow of gastric,colorectal and pancreatic cancer patients

The prognosis of digestive cancers is poor mainly due to intraperitoneal relapse by cells which may have already been seeded at the time of surgery. Using immunocytology we investigated the peritoneal cavity and, as a comparison, the bone marrow of 147 patients with gastric, colorectal and pancreatic cancer for micrometastatic cells. Cytological samples from peritoneal cavity lavages and bone marrow aspirates were analyzed using monoclonal antibodies (MAbs) against tumor-associated antigens (TAA) (CEA, CA-19-9, 17-1-A, C-54-0, Ra96) and compared to a MAb staining cytokeratins (KL-I). Patients with benign diseases served as controls. Intraperitoneal micrometastatic cells were detected in 27% of colorectal, 43% of gastric and 58% of pancreatic cancer patients. In the bone marrow, the corresponding data were 29% for colorectal, 25% for gastric and 58% for pancreatic cancer patients. Combined evaluation of both compartments increased the detection rate significantly (colorectal cancer: 40%, gastric cancer: 52%, pancreatic cancer: 72%). No unwarranted reactions were found in the control group. Combining 3 antibodies (CA-19-9, Ra96, C-54-0) enabled good detection for peritoneal cavity samples. In the bone marrow, the use of 2 antibodies (KL-I and CA-19-9) detected 94% of all positive samples, whereas KL-I and CA-19-9 stained approx. 70% of all positive samples in each case. The occurence of stained cells in the peritoneal cavity correlated with classical prognostic factors (TNM classification). © 1994 Wiley-Liss, Inc.     

Cellular fibronectin concentration in the plasma of patients with malignant and benign diseases: a comparison with CA 19-9 and CEA.

EDAcFN enzyme immunoassay (EIA) is a new tumour marker assay measuring the extra domain A-containing isoform of cellular fibronectin (cFN), a component mainly found in extracellular matrices. The concentration cFN was measured in plasma and serum from 468 patients with malignant and benign diseases. The concentrations of cFN were higher in plasma than in serum. Using receiver operating characteristic (ROC) curve analysis, determination from plasma was superior to serum at specificity levels higher than 78% and was chosen for further analysis. The highest frequencies of elevated cFN values were seen in patients with hepato-pancreato-biliary malignancies (50-67%). In pancreatic and bile duct cancers, cFN provided little further information to that obtained by CA 19-9. The greatest advantage over CA 19-9 and CEA was seen in patients with local colorectal cancer and in hepatocellular carcinomas. Four out of nine patients with Dukes'' stage B colorectal cancer had an elevated cFn level, but only one had an abnormal CEA level. In hepatocellular carcinomas, cFN was also compared with alpha-fetoprotein. The sensitivity of cFN (72%) was superior to that of AFP (61%), and concomitant use of cFN and AFP raised the sensitivity to 83%. The highest frequencies of elevated values in patients with benign diseases were observed in those with severe liver disease (32%) and biliary (17%) and pancreatic (24%) diseases. A combination of cFN and CA 19-9 showed the highest overall sensitivity of 47%, compared with 31% for cFN and 33% for CA 19-9. The corresponding specificities were 76% for cFN +/- CA 19-9, 85% for cFN and 83% for CA 19-9. The accuracy of a combination of cFN and CA 19-9 or CEA (60% respectively) was higher than that of cFN (55%), CA 19-9 (55%) or CEA (45%) alone. In conclusion, the results of the new cFN test are encouraging and further studies on larger patient materials have been started.     

Tumor markers of pancreatic cancer

To determine the clinical usefulness for diagnosis and monitoring of pancreatic tumor markers, serum levels of CA 19-9 (RIA; less than or equal to 37U/ml), POA (EIA; less than 11 U/ml), CEA (EIA; less than or equal to 4.4 ng/ml) and TPA (RIA; less than or equal to 110 U/ml) were measured in 57 patients with pancreatic cancer and 25 patients with benign diseases of the pancreas. Frequencies of elevation for pancreatic cancers were 73.9% for CA 19-9, 69.2% for POA, 48.9% for CEA and 73.2% for TPA. Furthermore, the frequencies of elevation at relatively early stages of pancreatic cancer were not high. It was therefore thought that these markers were unsuitable for early diagnosis of pancreatic cancers. Although serum levels of CA 19-9 and POA in cases of pancreatic cancer were distributed up to on extremely high level, those for benign diseases of the pancreas were located up to twice the values of the cut-off levels. Therefore, these two markers seem promising for differentiating preoperatively between pancreatic cancer and benign diseases of the pancreas. CA 19-9 and POA were also useful for monitoring the recurrence of pancreatic cancer. In particular, patients with high preoperative levels seem good candidates for postoperative monitoring.     

Comparative study of CA242 and CA19-9 for the diagnosis of pancreatic cancer.

A comparative study of a new tumour marker, CA242, and CA19-9 was conducted with special reference to their diagnostic usefulness in pancreatic cancer. CA242 showed sensitivity similar to that of CA19-9 for overall cases and early cases (stage I tumour) of pancreatic cancer. For other malignancies, the positive rates of CA242 were lower than those of CA19-9 except for colorectal cancer. An important characteristics of CA242 was that it was only slightly and infrequently elevated in the sera of patients with benign diseases such as chronic pancreatitis, chronic hepatitis and liver cirrhosis. This characteristic was more apparent in the patients with benign obstructive jaundice, indicating that the serum level of this marker was scarcely affected by cholestasis. Using cut-off levels corresponding to a 90% specificity, the clinical results obtained with CA242 in the diagnosis of pancreatic cancer were similar to those obtained with CA19-9, except that CA19-9 was falsely negative in some patients with early-stage pancreatic cancer. These findings suggest the usefulness of this marker for screening pancreatic cancer in patients on their first hospital visit. However, CA242 was found to be influenced by the Lewis blood group system. This unfavourable result is attributed to the C241 catcher antibody of this assay system, which has almost the same epitope specificity as the C50 and the NS19-9 monoclonal antibodies. In conclusion, CA242 is superior to CA19-9 in diagnosing pancreatic cancer by virtue of its higher specificity.     

CA 19-9 and CA 50 in benign and malignant pancreatic and biliary diseases

Serum concentrations of the CA 19-9 and CA 50 antigens were determined in 129 patients with malignant and benign biliary and pancreatic diseases. Values for the two markers were highly correlated (P less than 0.001). The concentrations of CA 19-9 and CA 50 were positive in 84.6% and 80.7% of patients with pancreatic cancer, respectively. The overall specificity of CA 19-9 (92.4%) was slightly higher than that of CA 50 (88.5%). The sensitivity of CA 50 (91.3%) was greater than that of CA 19-9 (73.9%) in patients with diseases of the biliary tract. Elevated concentrations of CA 19-9 (12.9%) and CA 50 (35.2%) were also found in a number of cases with benign disease, especially in patients with obstructive jaundice. These data suggest that both CA 19-9 and CA 50 can be useful markers of pancreatic cancer in nonjaundiced patients. The joint use of the two markers does not yield a better diagnostic resolution than the use of either one alone.     

Determination of serum DU-PAN-2 by enzyme immunoassay in patients with various digestive cancers

In order to evaluate the usefulness of serum DU-PAN-2, we determined this antigen in 384 patients with various malignancies and in 215 patients with benign diseases using a sandwich enzyme immunoassay system (Kyowa Medex Co.). Elevated DU-PAN-2 levels (greater than 400 U/ml) were observed in 55% of hepatocellular cancers, 50% of pancreatic cancers, and 43% of biliary tract cancers. On the other hand, most false-positive cases with benign diseases were observed in patients with liver injury, especially in the acute phase of acute hepatitis, chronic active hepatitis, and liver cirrhosis. However, in only a few cases with other benign diseases including pancreatitis, increased levels were found. Moreover, among the pancreatic cancer or biliary tract cancer patients studied, DU-PAN-2 was positive in 7 of the 19 CA 19-9-negative (less than 37 U/ml) patients and 32 of the 68 CEA-negative (less than 5 ng/ml) patients. These results indicate that the assay of DU-PAN-2 by EIA may have diagnostic usefulness in digestive cancer, especially pancreatic cancer or biliary tract cancer.     

Activation of telomerase and its diagnostic application in biopsy specimens from biliary tract neoplasms.

BACKGROUND: Telomerase activity has been reported to have potential as a useful diagnostic marker for cancer in various organs. The authors previously reported that telomerase activity in pancreatic juice differentiates pancreatic ductal carcinoma from adenoma and pancreatitis. In the current study, the usefulness of semiquantitatively determined telomerase activity in the diagnosis of malignant biliary tract neoplasms was investigated. METHODS: The samples examined included 61 surgically resected biliary tract tissues (11 gallbladder carcinomas, 5 bile duct carcinomas, 1 gallbladder adenoma, 30 cholecytitis cases, 7 cholesterol polyps, 1 normal gallbladder, and 6 normal common bile duct tissues), 42 bile samples from patients with biliary tract or pancreatic disease (19 cases of malignant biliary tract disease, 11 cases of benign biliary tract disease, 10 cases of malignant pancreatic disease, and 2 cases of benign pancreatic disease), and 14 bile duct biopsy specimens collected by percutaneous transhepatic choledochoscopy or endoscopic retrograde cholangiopancreatography (8 bile duct carcinoma specimens, 1 bile duct adenoma specimen, and 5 hepatolithiasis specimens). RESULTS: In biliary tract tissues, a telomerase ladder was detected in 73% of gallbladder carcinomas, 40% of bile duct carcinomas, and none of the other biliary tract tissues. One gallbladder adenoma showed a weak telomerase ladder. The telomerase ladder was detected in the bile sample from 1 patient (5.3%) with malignant biliary tract disease, none of the patients with benign biliary tract disease, 5 patients (50%) with malignant pancreatic disease, and none of the patients with benign pancreatic disease. In biopsy specimens, the telomerase ladder was detected in 75% of patients with bile duct carcinoma but not in any of the patients with hepatolithiasis. The median value of relative telomerase activity in the patients with bile duct carcinoma was significantly higher than that in the patients with hepatolithiasis. The diagnosis of bile duct carcinoma was confirmed preoperatively by histopathologic examination in only 25% of the biopsy specimens. CONCLUSIONS: The results of the current study indicate that telomerase is highly activated in biliary tract carcinomas and that the detection of a telomerase ladder in biopsy samples is an excellent tool for the diagnosis of bile duct carcinomas.     

Clinical evaluation of CA-50 in cases with colorectal cancer

Serum CA-50 has been evaluated in 67 healthy donors and in 46 patients with a colorectal cancer by an enzyme immunoassay (EIA Kit, Mitsui pharmaceuticals, Inc.). The mean value of the healthy donors (n = 67) was 10.6 +/- 6.1 U/ml and for patients with a colorectal cancer 31.7 +/- 55.2 U/ml. Both in healthy donors and in patients, the mean value was found to be higher in females than males. The overall sensitivity in the colorectal cancer patients was 26.1 percent, the percentages for those in stage I, 20, II, 9.1, III, 40, IV, 20, and V, 50% respectively. In a correlation between serum CA-50 and CA 19-9, the correlation coefficient was 0.82 (p less than 0.01), and in between CA-50 and CEA, 0.51 (p less than 0.01). Thus a combination assay among CA-50, CA 19-9, and CEA has proved to be of significant value in cases of a colorectal cancer.     

CA19-9和CA242对消化道肿瘤的诊断价值

目的研究肿瘤标志物CA19-9与CA242对消化道肿瘤的诊断价值。方法对87例消化道恶性肿瘤及90例消化道良性疾病患者进行血清CA19-9与CA242检测。结果CA19-9和CA242对胰腺癌、胆系癌有较高的阳性率,其诊断的灵敏度、特异度如下CA19-9对胰腺癌分别为84.7%和74.5%,对胆系癌分别为80%和74.5%;CA242对胰腺癌分别为66.7%和80%,对胆系癌分别为60%和80%。其它恶性肿瘤,除结肠癌外,CA19-9的阳性率均高于CA242。原发性肝癌患者血清CA19-9和CA242阳性率具有显著差异,分别为66.7%和37%,而良性肝病患者血清CA19-9和CA242阳性率分别为50%和26.8%,CA242较少受慢性肝病的影响。结论CA19-9和CA242可用于胰腺癌、胆系癌的诊断,CA242对良恶性肝病具有一定的鉴别诊断作用,并对结直肠具有一定的诊断价值。     

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.     

Tissue expression of the tumour associated antigen CA242 in benign and malignant pancreatic lesions. A comparison with CA 50 and CA 19-9

The expression of a novel tumour associated antigen CA 242, defined by the monoclonal antibody C 242, was studied by immunoperoxidase staining in formalin-fixed, paraffin-embedded tissue sections from normal pancreata, pancreata with pancreatitis and benign and malignant pancreatic neoplasms. The antigenic determinant of the C 242 antibody is a sialylated carbohydrate structure, related but chemically different from tumour marker antigens CA 19-9 and CA 50. Thirty-eight of 41 (93%) well to moderately differentiated ductal adenocarcinomas of the pancreas and all cystadenocarcinomas were positive for CA 242. The staining was most intense in the apical border of the cells, and in the intraluminal mucus. Only two out of seven poorly differentiated adenocarcinomas stained, and the number of positive cells was smaller than in well differentiated carcinomas. Only occasional cells were stained in one out of five anaplastic carcinomas. Part of large ducts were positive in 91% (21/23) specimens of chronic pancreatitis. In acute pancreatitis small terminal ducts, centro-acinar cells and some large ducts stained for CA 242. In normal pancreas only a few small terminal ducts were CA 242 positive. Carcinomas always stained more strongly for CA 242 than normal pancreatic tissue adjacent to the carcinoma. The results of CA 242 are compared with those of tumour marker antigens CA 50 and CA 19-9. Serum CA 242 levels were determined in 23 of the patients with pancreatic cancer using a fluoroimmunoassay. Fifteen (65%) patients had an elevated value. There was no clear-cut correlation between the serum levels and the immunohistochemical expression of the CA 242 antigen. The expression of CA 242 in pancreatic tissue resembles that of CA 50 and is similar to CA 19-9. The antigen is expressed in serum of many patients with pancreatic cancer and, therefore, is a potential candidate for a serum tumour marker.