Comparison of CA-50, a new tumour marker, with carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in patients with gastrointestinal diseases

Serum levels were determined in 434 patients with benign and malignant gastrointestinal diseases and compared with the serum concentrations of carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). The highest proportion of elevated CA-50 levels (greater than 17 U ml-1) was found in patients with pancreatic cancer (73%). High levels were mainly associated with advanced cancer, but also half of the patients with a resectable pancreatic tumour had an increased CA-50 concentration. The CA-50 level was elevated in 37-58% of patients with colorectal, gastric, hepatocellular and biliary tract cancers. In all gastrointestinal cancers, CA-50 gave additional information compared with CEA and AFP, except in hepatocellular carcinoma where AFP was the best marker.     

Evaluation of des-gamma-carboxy prothrombin as a marker protein of hepatocellular carcinoma

We measured des-gamma-carboxyglutamic acid prothrombin (protein induced by vitamin K absence or antagonist-Factor II: [PIVKA-II]) in plasmas of normal subjects, patients with thrombotic disease, those with hepatic disease including hepatocellular carcinoma, and those with carcinoma of other tissues, and compared the results with results of blood coagulation tests used for the examination of hepatic function. In addition, in the patients with hepatic disease, PIVKA-II and alpha-fetoprotein (AFP) levels were compared. The PIVKA-II level was frequently high in patients with thrombotic disease given warfarin therapy and those with hepatocellular carcinoma. However, in patients with thrombotic disease who were not given warfarin therapy, no significant correlation was seen between the PIVKA-II value and the results of the thrombotest or hepaplastin test, suggesting no association between the PIVKA-II level and the degree of impairment of hepatic function. In 70 patients with hepatocellular carcinoma, the percentage of patients positive for PIVKA-II (greater than or equal to 0.1 micrograms/ml) and those positive for AFP (greater than or equal to 20 ng/ml) were similar (77% and 74%, respectively). Pearson's correlation of coefficient between the PIVKA-II value and the AFP value in the 70 patients was 0.463. However, false-positive rates in patients with hepatic disease other than hepatocellular carcinoma were lower for PIVKA-II. Combined assessment of PIVKA-II and AFP increased positive rates and allowed exclusion of false-positive patients. The plasma PIVKA-II level is suggested to be useful as an indicator of warfarin control in patients with thrombotic disease, as a marker of hepatocellular carcinoma, and is particularly of value when assessed in combination with AFP.     

Thyroxine-binding globulin as a marker of liver tumors

This investigation was undertaken to evaluate the level of thyroxine-binding globulin (TBG) as a marker of liver tumors. TBG examination was performed on 42 patients with primary hepatocellular carcinoma (PHC) and 50 postoperative patients with metastases to the liver. alpha-Fetoprotein (AFP) and carcinoembryonic antigen (CEA) concentrations were determined at the same time. AFP was positive in 90.5% of the patients with PHC, and TBG was higher than normal in 69% of patients with PHC. In the 50 patients with liver metastasis, the TBG was higher than normal in 72%, and CEA was also increased in 64%. CEA was negative in 18 of 50 patients with liver metastasis. On the other hand, of the 18 CEA-negative patients, 14 (77.8%) had a higher than normal TBG concentration. This was a significant, but not specific, increase. Therefore, elevated TBG levels are a sensitive, although nonspecific, tumor marker to determine the presence of liver tumors, especially in cases of metastasis to the liver.     

Value of serum alpha-fetoprotein and ferritin in the diagnosis of hepatocellular carcinoma

Alpha-fetoprotein (AFP) and ferritin in the serum were determined by radioimmunoassay and enzyme immunoassay, respectively, in 224 healthy subjects, 55 patients with benign hepatic disease and 44 patients with hepatocellular carcinoma (HCC). The AFP levels in the serum were significantly higher in patients with HCC than in healthy subjects and in patients with benign hepatic disease, but this level was not a satisfactory indicator of small HCC since it was elevated in only 75.0% of the patients with a tumor of less than 3.0 cm in its greatest diameter. Although serum ferritin was elevated in only 56.8% of the patients with HCC, the combination of these two tests raised the diagnostic rate of HCC from 65.9% by serum AFP measurement alone to 88.6% with no appreciable decrease in the specificity for HCC. In particular, it raised the diagnostic rates of lesions of less than 3.0 cm in the greatest diameter from 75.0% by measuring AFP alone to 100%. Thus the combination of AFP and ferritin measurement in the serum is useful for the early detection of HCC.     

Do CA 19-9 and TPA play a minor role as compared to AFP in diagnosing primary hepatocellular carcinoma?

This study was undertaken in order to compare the ability of 4 tumour markers to discriminate between liver cirrhosis patients with or without hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA 19-9 and tissue polypeptide antigen (TPA) were determined in 63 patients with liver cirrhosis and in 25 patients with HCC in liver cirrhosis. All 4 serum markers were found to be increased in a number of liver cirrhosis patients, regardless of the presence of HCC. AFP was found to be more elevated in HCC patients as compared to the other group; no difference was observed for CA 19-9, CEA and TPA. A significant correlation was detected in HCC patients between AFP and TPA. Significant correlation were detected in all except HCC patients between liver function tests and TPA. We can conclude that AFP determination remains as yet the only suitable marker able to detect HCC in liver cirrhosis. The newly introduced serum marker CA 19-9 is, as previously reported, unhelpful for CEA. TPA can in some instances (i.e. in the absence of an important hepatic cell necrosis or cholestasis) provide a clue to neoplastic growth.     

血AFP、CEA、CA-50、CA-199联合检测对原发性肝癌的诊断价值

目的　探讨肿瘤标志物AFP、CEA、CA -5 0、CA -199联合检测对原发性肝癌的诊断价值。方法　选择原发性肝癌 32例 ,行血清AFPRIA、CEARIA、CA -5 0IRMA、CA -199IRMA检测。结果　原发性肝癌 32例血AFP、CEA、CA -5 0、CA -199四项联合检测阳性符合率 10 0 % ,而各单项检测AFP为 6 8 8% (P <0 0 1) ,CEA 15 6 % (P <0 0 0 1) ,CA -5 0 78 1% (P <0 0 5 ) ,CA -19975 % (P <0 0 5 )。在原发性肝癌AFP阴性 10例中 ,血CEA值增高 2例 (2 0 % ) ,血CA -5 0值增高 9例 (90 % ) ,血CA -199值增高 8例 (80 % )。结论　血AFP、CEA、CA -5 0、CA -199四项标志物联合检测优于各单项检测 ,CA -5 0、CA -199对血AFP阴性原发性肝癌阳性符合率高 ,血CEA原发性肝癌诊断性符合率低 ,诊断意义较小。     

血清AFP、CA125、CA199和CEA联合检测在原发性肝癌诊断中的价值

目的 通过联合检测血清AFP、CA125、CA199、CEA四种肿瘤标志物的含量,观察其对原发性肝癌(PHC)的诊断价值.方法 运用电化学发光免疫分析的方法,检测PHC组68例、良性肝病组50例及健康对照组58例血清中AFP、CA125、CA199、CEA的含量,分析各肿瘤标志物的灵敏度、特异性、准确度及联合检测的临床意义.结果 单独检测AFP、CA125、CA199、CEA对PHC的诊断阳性率分别为76.4%、35.3%、44.1%、29.4%;联合检测四种肿瘤标志物的阳性率为94.1%.结论 四种肿瘤标志物的联合检测有助于提高PHC患者的诊断阳性率.     

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.     

Alpha-fetoprotein (AFP) Elevation Gastric Adenocarcinoma and Importance of AFP Change in Tumor Response Evaluation

Background: Elevated serum alpha-fetoprotein (AFP) levels in adults are considered abnormal. This parameteris used mostly in the diagnosis and follow-up of hepatocellular carcinomas and yolk sac tumors. Among the otherrare tumors accompanied with elevated serum AFP levels, gastric cancer is the most common. In this study, weevaluated the follow-up and comparison of the treatment and marker response of patients with metastatic gastriccancer who had elevated serum AFP levels. Materials and Methods: We performed a retrospective study, includingall consecutive patients with advanced gastric cancer, who received systemic chemotherapy with elevated AFPlevel. Results: Seventeen metastatic gastric cancer patients with elevated AFP levels at the time of diagnosis wereevaluated. Fourteen (82.4%) were males and three (17.6%) were females. The primary tumor localization wasthe gastric body in 8 (76.4%), cardia in 7 (41.2%), and antrum in 2 (11.8%). Hepatic metastasis was observed in13 (76.4%) at the time of diagnosis. When the relationship of AFP levels and carcinoembryonic antigen (CEA)response of the patients with their radiologic responses was evaluated, it was found that the radiologic responsewas compatible with AFP response in 16 (94.1%) patients and with CEA response in 12 (70.6%); however, in 5(29.4%) patients no accordance was observed between radiological and CEA responses. Conclusions: Followupof AFP levels in metastatic gastric cancer patients with elevated AFP levels may allow prediction of earlytreatment response and could be more useful than the CEA marker for follow-up in response evaluation.     

Serum levels of CA 125 in patients with gastrointestinal cancers

Serum levels of CA 125 and markers reputed as specific for cancers in relevant locations (squamous cell carcinoma, SCC, carcinoembryonic antigen, CEA, CA 19.9, alpha-fetoprotein, AFP) were determined in 107 patients with gastrointestinal (GI) carcinomas. The aim of this study was to assess their individual and combined sensitivities, and the power of CA 125 in excluding primary ovarian epithelial cancer from GI primary. Serum CA 125 levels (in U/ml) ranged from nondetectable to 400 in patients with esophageal, to 570 in those with gastric, and to 300 in patients with colorectal carcinoma. The levels for liver secondaries, pancreatic, and hepatocellular carcinoma were 480, 2,720 and 1,100 U/ml, respectively. Serum SCC antigen was elevated in all patients with esophageal cancer, CEA or CA 19.9 in 52% of patients with gastric cancer and in 63% with liver secondaries, and CEA in 95% of patients with colorectal cancer; whereas serum CA 125 above 65 U/ml was found in 25% of this subgroup, but only in those with already an elevated concentration of specific marker(s). Serum CEA or CA 19.9 was elevated in 71%, CA 125 in 59% of patients with pancreatic cancer; the latter mostly in those with already elevated CEA or CA 19.9. Serum AFP was elevated in 84% and CA 125 in 40% of patients with hepatoma; the latter mostly in those with already an elevated AFP. CA 125 values exceeding 1,000 U/ml were found in 1 patient with pancreatic cancer (2,720 U/ml) and in 2 with hepatoma (1,050 and 1,100 U/ml). These findings illustrate the nonspecificity of the CA 125 antigen, its small if any advantage compared to the specific markers, and they diminish its role as a marker for primary ovarian cancer from GI primary unless it exceeds 2,800 U/ml.     

Neuron-specific enolase (NSE) as a tumour marker and comparative evaluation with carcinoembryonic antigen (CEA) in small-cell lung cancer

Serum neuron-specific enolase (NSE) was evaluated in a number of malignant tumours. It was elevated (greater than 12.5 micrograms l-1) in 13/17 (76.5%) patients with extensive small-cell lung carcinoma and in none of the three patients with limited disease. Of patients with carcinoma of the breast 4/12 (33.3%) had elevated concentrations. Normal concentrations were found in patients with non-Hodgkin's lymphoma (19) and Hodgkin's disease (15), carcinoma of the cervix (2), CSF and serum (5) of patients with gestational trophoblastic disease (with definite nervous system involvement). Comparative serial studies of NSE and carcinoembryonic antigen (CEA) concentrations were done in 15 patients with small-cell lung cancer (SCLC). Of these 7/15 (46.7%) had elevated pre-treatment concentrations of both CEA and NSE, 1/15 (6.7%) had CEA elevated only, while 2/15 (13.3%) had NSE alone elevated. Of those patients with normal pre-treatment marker concentrations 3/5 (60%) had elevated markers on recurrence. The mean survival period was 61.9 weeks; 66.8 weeks for the marker-negative group and 44.6 weeks for the marker-positive (both NSE and CEA) group. Combined NSE and CEA evaluation provide additional means of monitoring SCLC.     

Transforming growth factor-beta1 as a useful serologic marker of small hepatocellular carcinoma

BACKGROUND: Although alpha-fetoprotein (AFP) is a useful serologic marker of hepatocellular carcinoma (HCC), it has been reported insufficiently sensitive in detecting small HCCs. Plasma transforming growth factor-beta1 (TGFbeta1) has been reported to be elevated in HCC patients compared with liver cirrhosis patients. It has been reported that TGFbeta1 mRNA was overexpressed in HCC, especially in patients with small HCC and well-differentiated HCC compared with patients with liver cirrhosis. The current study investigated the usefulness of TGFbeta1 compared with AFP in the diagnosis of small HCCs. METHODS: Thirty-eight patients with small HCC (< or = 3 cm), 31 patients with liver cirrhosis only, and 23 normal volunteers were studied. Using plasma TGFbeta1 and serum AFP levels measured at the time of diagnosis, the sensitivities and specificities were calculated in the diagnosis of small HCCs. RESULTS: Plasma TGFbeta1 and serum AFP levels were significantly higher in patients with small HCC than in those with liver cirrhosis. In diagnosing small HCCs, the cut-off values of plasma TGFbeta1 and serum AFP were 800 pg/mL and 200 ng/mL, respectively, where the specificities were over 95%. At the cut-off level of plasma TGFbeta1 and serum AFP, the sensitivities were 68% and 24%, respectively. CONCLUSIONS: The current results suggest that TGFbeta1 may be a useful serologic marker in detecting HCCs earlier because it shows higher sensitivity than, with specificity as, AFP in the diagnosis of small HCCs.     

Alpha-fetoprotein and carcinoembryonic antigen in pancreatobiliary disease with and without jaundice

A comparative study of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in serum was made by radioimmunoassay in 66 patients with pancreatobiliary disease with and without obstructive jaundice. biliary concentrations of these proteins were assayed in 12 patients with benign and 7 patients with malignant disease. There was no statistical difference in serum AFP between these two groups but there was a difference in serum CEA. Although CEA and AFP in bile in both groups were higher than in serum there was no statistical difference in serum CEA and AFP in patients with and without obstructive jaundice in either benign or malignant disease. In benign disease, patients with inflammation had higher serum CEA than normal. Although there was no statistical difference in serum CEA in patients with a without liver metastases, the serum CEA in liver metastases was significantly higher than in benign disease. We concluded that AFP is unlikely to be important in the assessment or management of patients with cancers other than those derived from the liver or yolk sac, and that the elevation of serum CEA in patients with malignant pancreatobiliary disease either with or without obstructive jaundice occurs mainly in the presence of widespread malignancy, especially in liver metastases.     

Carcinoembryonic antigen and alpha fetoprotein in malignant tumors of the female genital tract.

Circulating carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) levels were measured by radioimmunoassay in 53 patients with carcinoma of the ovary, 16 patients with other malignant genital tumors, and 31 women with nonmalignant diseases of the genital tract. The serum CEA concentration was elevated (greater than 5 ng/ml) in 11 patients with ovarian cancer, 2 patients with endometrial cancer, 1 patient with carcinoma of the cervix, and 1 patient with a benign embryonal cystic teratoma. Elevated CEA levels were found only in patients with advanced malignant disease, while early stages were associated with normal CEA concentrations. AFP levels were normal in all but 1 patient. Both CEA and AFP levels were markedly raised in a case of advanced genital carcinoma arising probably from the ovary. Ascitic fluid of another patient with ovarian cancer contained a high concentration of CEA, giving an identical reaction in immunodiffusion with CEA from colon cancer. The present results indicate that while the increased expression of carcinofetal components takes place in some malignant tumors of the female genital tract, it is usually a late phenomenon.     

Clinical usefulness of serum procollagen-III-peptide in patients with solid tumor

An attempt has been made to determine the clinical usefulness of serum procollagen-III-peptide (P-III-P) in comparison with serum CEA and AFP in patients with solid tumor. Serum P-III-P levels were measured in 82 cases of carcinoma and 64 cases of benign disease employing an AG Radiochemishes Laboratrium RIAgnost P-III-P kit. Serum P-III-P levels of 148 healthy subjects were 8.5 +/- 2.6 ng/ml (M +/- S.D.), with an upper limit of 13.7(M + 2S.D.). The serum P-III-P level in cases of hepatocellular carcinoma was elevated to 47.5 +/- 97.5 (88.9%). Serum P-III-P levels in cases of pancreatic carcinoma were elevated slightly, whereas those for patients with carcinoma of the stomach, colorectum, esophagus, and breast were low, and their P-III-P positive rates were lower than those of their serum CEA. On the other hand, the serum P-III-P levels in benign diseases involving the liver and biliary tract were higher than those in other benign diseases. Therefore, although serum P-III-P can be a useful marker in hepatocellular carcinoma, it may possibly be difficult to discriminate it from benign diseases involving the liver and biliary tract.     

Alpha-1 antitrypsin (AAT) and alphafoetoprotein (AFP) in sera of patients with germ-cell neoplasms: value as tumour markers in patients with endodermal sinus tumour (yolk sac tumour).

Serum alphafoetoprotein (AFP) and serum alpha-1 antitrypsin (AAT) were determined in 24 patients with germ-cell neoplasms of the gonads and extragonadal sites and in two patients with hepatocellular carcinoma. In the majority of the patients serial determinations were performed. All seven patients with testicular seminoma and four patients without evidence of active disease had normal levels of serum AAT and AFP. The remaining 13 patients with germ-cell neoplasms had tumours containing endodermal sinus tumour (yolk-sac tumour) elemetns. All these 13 patients had elevated levels of serum AFP and the levels were high or very high in most cases. Nine of these 13 patients had raised serum AAT, although the elevation above normal levels was only slight in a number of cases. When serial determinations were performed serum AAT levels frequently followed the pattern of serum AFP levels, but the AAT levels were frequently within normal limits and therefore the interpretation of the results was difficult, and much less reliable as compared with those for serum AFP. The elevation of serum AAT levels following the recurrence of the tumour was found to occur much later and was much less marked than elevation of serum AFP, which occurred early, showed a large rise and was a reliable marker of tumour recurrence in patients with germ-cell neoplasms containing endodermal sinus tumour elements. It is therefore considered that, although there is good evidence that serum AAT is produced by endodermal sinus tumour elements, serum AAT is not a useful monitor of disease activity in these patients, especially when compared with serum AFP, the value of which is well recognized. Serum AAT may be a useful tumour marker in patients with hepatocellular carcinoma, and this aspect should be investigated further.     

Multiple biochemical markers in patients with gynecologic malignancies

Plasma levels of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) were measured in 253 patients with gynecologic malignancies and in 317 patients with benign gynecologic diseases. Plasma concentrations of each of these antigens were elevated in a significantly (p less than 0.001) greater number of patients with invasive gynecologic cancers than in the control population. Carcinoembryonic antigen was the most commonly elevated marker, followed by AFP and hCG. Prior to therapy, over 85% of patients with ovarian or cervical cancer had elevated plasma levels of one or more antigens. Specifically, CEA was most often elevated in patients with mucinous adenocarcinomas of the ovary and endocervix. Alpha-fetoprotein was most often increased in patients with germ cell or stromal tumors of the ovary and in patients with large-cell nonkeratinizing cervical cancers. In contrast, hCG concentrations were highest in patients with serious cystadenocarcinomas of the ovary and in patients with keratinizing squamous cell carcinomas of the cervix. Plasma antigen levels were directly related to tumor differentiation and stage of disease, and generally returned to normal eight to 12 weeks following therapy. Effective plasma and tumor antigen screening during initial evaluation of patients with gynecologic tumors should help to identify the most appropriate antigen for immunodetection procedures and for serial plasma determinations following therapy.     

Evaluation of CA 125 as a serum marker of hepatocellular carcinoma

Serum CA 125 concentrations were raised in 90.4% of 115 southern African black patients with hepatocellular carcinoma. Seventy-four percent of 62 patients with amebic hepatic abscess, 60% of 40 patients with chronic hepatic parenchymal disease (chronic hepatitis or cirrhosis), and 60.9% of 41 patients with acute viral hepatitis also had raised values. The median serum CA 125 concentration for patients with hepatocellular carcinoma differed significantly from the benign hepatic disease groups analysed (p less than 0.0002). Serum alpha-fetoprotein levels were raised in 90.4% of the 115 hepatocellular carcinoma patients. CA 125 is thus a highly sensitive marker for hepatocellular carcinoma, but lacks specificity.     

Alpha-fetoprotein in the woodchuck model of hepadnavirus infection and disease: normal physiological patterns and responses to woodchuck hepatitis virus infection and hepatocellular carcinoma.

Persistent infection of the eastern woodchuck (Marmota monax) with the woodchuck hepatitis virus (WHV) produces disease sequelae similar to those observed in humans with persistent hepatitis B virus infection, including hepatocellular carcinoma (HCC). To further characterize serological markers of HCC in the woodchuck, serum alpha-fetoprotein (AFP) was measured under normal physiological conditions and following infection with WHV. Serum AFP was elevated in association with WHV-induced hepatitis and HCC and was a useful indicator of hepatic responses in individual animals throughout the course of experimental WHV infection. The frequent occurrence of normal elevations in serum AFP during the fall and winter, however, limits the use of AFP as a marker for early detection of HCC. The present temporal studies of AFP responses in WHV-infected woodchucks have identified several stages of infection where virological and cellular interactions can be investigated at the molecular level. Studies of AFP in the woodchuck model should provide opportunities to further elucidate the physiological and immunological functions of AFP and to understand virus-host cell interactions during the course of experimental hepadnavirus infection leading to HCC.