Patterns of seminoma tissue markers and deletions

Seminomas and control tissues were analyzed for several tumor markers. Very high levels of placental alkaline phosphatase (PLAP)-like enzyme levels were found in all 18 seminomas studied. The majority of the seminomas were of phenotype I, thus differing from palcental PLAP. The mean amount of enzyme protein as measured by monoclonal antibodies, was 100 times higher than in non-malignant tissues and 10 times lower than in placental tissue. The specific enzymatic activity in seminomas was about half of that observed in placenta. Similarly, the specific activity of PLAP-like enzymes in sera of patients with seminoma was only about half of that found in pregnancy sera. HCG was strongly elevated in 3 seminomas, but not obviously related to PLAP. Thirteen of the 17 pure seminomas had HCG over 100 IU/g, which was not seen in normal testes. Liver alkaline phosphatase (LAP) and intestinal alkaline phosphatase (IAP) were high in seminomatous tissues, the mean increases being 60-fold and 20-fold, respectively. The highest IAP levels were found in 2 yolk-sac tumors. Ferritin was moderately elevated in seminomas, but high in several control tissues. Carcinoembryonic antigen (CEA) was not elevated and alpha-fetoprotein (AFP) was not detected at all in pure seminomas. A decrease in carbohydrate antigen 50 (CA-50) content was noted in seminomas as compared to normal testes, yolk-sac tumors and choriocarcinomas. Defects in tumor-related enzymes may account for increase of PLAP and decrease of CA-50.     

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.     

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.     

Tumor Markers in Colorectal Carcinoma An Evaluation of Carcinoembryonic Antigen, Tissue Polypeptide Antigen, Placental Alkaline Phosphatase and Pseudouridine

The biologic markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), placental alkaline phosphatase (PLAP) and pseudouridine were analysed in 37 patients with colorectal carcinoma. CEA, TPA and PLAP were derived from the serum and pseudouridine from the urine. The incidence of all four markers increased with advancing stages of the disease. Patients with distant metastases had elevated levels of CEA, TPA, PLAP and pseudouridine in 85, 27, 18 and 33 per cent of the total cases, respectively. When survival was compared, patients with 2 to 4 elevated markers had shorter survival than those with none or only one elevated marker.     

Tumor markers in mammary carcinoma. An evaluation of carcinoembryonic antigen, placental alkaline phosphatase, pseudouridine and CA-50

In 104 patients with breast cancer, carcinoembryonic antigen (CEA), placental alkaline phosphatase (PLAP) and the carbohydrate antigen CA-50 were analysed in serum. Excretion of the modified nucleoside, pseudouridine, was analysed in urine. The patients were subdivided in three different clinical stages according to disease manifestations. Levels of CEA and pseudouridine correlated to clinical stage and 58 per cent of the patients with distant metastases had elevated levels of CEA, compared with 36 per cent for pseudouridine. For PLAP and CA-50, the levels did not show any clear correlation to clinical stage. Increased activity of PLAP correlated strongly to tobacco smoking. A decrease in the level of CEA was observed following radical mastectomy. Increase in CEA levels predicted relapse in 5 out of 14 patients within about 3 to 6 months. In patients with tumor manifestations, elevated CEA levels predicted an inferior prognosis compared to those with ordinary levels.     

Clinical usefulness of three monoclonal antibody-defined tumor markers: CA 19-9, CA 50, and CA 125

This article reviews the clinical usefulness of three monoclonal antibody-defined tumor markers: CA 19-9 or GICA, CA 50, and CA 125. These markers have been regarded as worthwhile tools for diagnosis and monitoring the management of patients with cancers in selected sites. The CA 19-9 test in combination with the CEA test is a useful adjunct for staging in some advanced cases and for monitoring therapy in the majority of patients with carcinoma of the stomach. Sensitivity of these assays performed concurrently is comparable to CEA alone in colorectal carcinoma. The CA 19-9 test alone is useful for staging and monitoring management of patients with carcinoma of the pancreas. In colorectal carcinoma the CA 19-9 test is redundant because of significantly lower sensitivity than that of the CEA assay; the latter remains the test of choice. The CA 50 test per se is redundant since the CA 19-9 antigen is the target for both the C50 MAb and the NS 19-9 MAb. The CA 125 test contributes to staging and is a useful adjunct for monitoring management of patients with non-mucinous carcinomas of the ovary. If positive after initial surgery and chemotherapy, this test provides evidence of the presence of residual or metastatic tumor and thus may obviate the need for second-look surgery. These conclusions are based on a review of recent relevant publications as well as on our own results obtained from preoperative evaluation and postoperative follow-up of about 600 patients with cancers in relevant sites.     

血清VEGF、CA19-9以及OPN水平检测在大肠癌的临床诊断和手术疗效分析中的应用

目的:探讨大肠癌患者手术前后血清VEGF、CA19-9和OPN的含量变化及其临床意义。方法:对50例大肠癌患者VEGF、CA19-9、OPN以及CEA 联合检测判断大肠癌阳性检出率,并测定术前、术后5天和术后10天血清血管内皮生长因子（VEGF）、糖蛋白抗原CA19-9以及骨桥素（OPN）的含量。结果:VEGF、CA19-9和OPN三者联合检测时大肠癌检出率高于单独检测CEA。手术后5天以及手术后10天患者血清中VEGF、CA19-9以及OPN水平与术前相比有明显降低（P＜0.05）。大肠癌TNM I和II期患者血清中三种肿瘤标志物含量明显低于III和IV期患者(P＜0.05);中-低分化（包括未分化）患者血清中VEGF、CA19-9以及OPN水平高于高分化患者,两组比较具有统计学意义（P＜0.05）。结论:血清VEGF、CA19-9和OPN水平可作为大肠癌临床分期、判断预后和恶性程度的依据,可作为大肠癌诊断、分期、预后判断的重要指标,值得临床推广应用。     

Increase in both CEA and CA19-9 in sera is an independent prognostic indicator in colorectal carcinoma

BACKGROUND AND OBJECTIVES: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) are well known to be the most common tumor markers of colorectal carcinomas. However, the significance of increase in these markers to predict the prognosis of the patients remains a problem for debate. METHODS: One hundred three patients with colorectal carcinoma, who had been treated by resection and reconstruction of digestive tracts were studied. Correlation of preoperative serum value of CEA and CA19-9 with clinicopathologic features including prognosis of the patients was investigated. RESULTS: Preoperative elevation of both of the two markers proved to be an independent prognostic indicator, however, an elevation of only one of the two markers did not obtain a prognostic significance. CONCLUSIONS: Combined data of preoperative increase in CEA and CA19-9 in sera can provide a powerful and useful information to predict prognosis of patients with colorectal carcinoma.     

Leukocyte alkaline phosphatase and carcinoembryonic antigen in colorectal cancer patients (usefulness in the assessment of the stage)

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

CA 19-9 As a Marker in Addition to CEA to Monitor Colorectal Cancer

BackgroundCarcinoembryonic antigen is the commonly used tumor marker in patients with colorectal cancer, and CA 19-9 might be an additional marker. The aim of this retrospective study was to investigate whether CA 19-9 levels can be used to monitor the disease process in patients with colorectal cancer who had no elevated CEA levels. The secondary aim was to determine if preoperative increased levels of CEA and CA 19-9 were associated with mortality.Materials and MethodsTwo sets of data from patients with histologically confirmed colorectal cancer, were included in a single-center study. First, patients with a minimum of 3 serial measurements of CA 19-9 and CEA tumor markers were related to the clinical course of their disease. Second, patients with preoperative levels of CEA and CA 19-9 were related to survival.ResultsIn patients with colorectal cancer and 3 serial measurements of tumor markers, 7.3% had only increased CA 19-9 levels without increased CEA levels, and 55.4% of the patients had an increase of CA 19-9 and CEA levels. In the patients with available preoperative markers, patients with only an increase of CA 19-9 had a significantly decreased 5-year survival compared with patients with an increase of only CEA (P = .013).ConclusionCA 19-9 can be used as additional marker to follow the disease process in patients with colorectal cancer without an increase in CEA level. Patients with preoperative increased CA 19-9 level had a poorer 5-year survival than patients with preoperative increased CEA levels.     

The Value of CA 19-9 in Gastric and Colorectal Carcinoma

We have conducted a prospective study of 441 patients, to investigate the utility of a new tumor marker CA 19-9 for the diagnosis and monitoring of patients with cancer of the gastrointestinal tract (93 patients with colorectal carcinoma, 57 with carcinoma of the stomach, 10 with esophageal carcinoma, 45 with malignancies outside the gastrointestinal tract, and 236 with benign general surgical disease). Results were compared to those obtained for carcinoembryonic antigen (CEA) in the diagnosis of carcinoma of the stomach and colon/rectum. CEA is more sensitive than CA 19-9 in all stages of carcinoma of the stomach and colon/rectum. During treatments of gastrointestinal carcinomas, CEA and CA 19-9 were determined at the same time in 66 and 165 patients with surgically treated carcinoma of the stomach and colorectal carcinoma, respectively. It was noted that CEA is more sensitive than CA 19-9 in detecting recurrence. However, CA 19-9 is more specific. The best results were obtained when both markers were used together.     

肿瘤标志物蛋白芯片中结直肠癌相关指标的筛选及优化

 目的　分析C12多肿瘤标志物蛋白芯片指标与结直肠癌的相关性，筛选结直肠癌相关指标，为建立结直肠癌小型诊断芯片提供依据。方法　使用C12多肿瘤标志物蛋白芯片系统，检测173例结直肠癌患者术前血清中12种常见肿瘤标志物（CA19-9、NSE、CEA、CA242、CA125、CA15-3、AFP、Ferritin、f-PSA、PSA、β-HCG及HGH）的水平，筛选结直肠癌相关指标，采用κ检验比较其与C12检测结果的一致性，并用成本-效果分析法，寻找最佳检测方案。结果　173例结直肠癌患者血清肿瘤标志物（TM）升高主要集中于4项指标：CEA（36.4 ％）、CA242（19.7 %）、CA19-9（18.5 %）、CA125（9.8 ％）；采用κ检验比较4项指标不同组合与C12的检测结果，得出一致性极强的小型方案有7种，使用成本-效果分析法得出最佳方案为CEA单项指标检测。结论　C12多肿瘤标志物蛋白芯片系统对结直肠癌的辅助诊断价值有限，各项指标联合未能明显提高结直肠癌检出率，且芯片设计复杂、成本较高。因此，有必要补充新的指标，设计小型芯片，增强其临床应用价值。     

Combined Detection of CEA,CA 19-9, CA 242 and CA 50 in the Diagnosis and Prognosis of Resectable Gastric Cancer

Our aim was to investigate the value of combined detection of serum  carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA 242 and CA 50 in diagnosis and assessment of prognosis in consecutive gastric cancer patients. Clinical data including preoperative serum CEA, CA 19-9, CA 242, and CA 50 values and information on clinical pathological factors were collected and analyzed retrospectively. Univariate and multivariate survival analyses were used to explore the relationship between tumor markers and survival. Positive rates of tumor markers CEA, CA 19-9, CA 242 and CA 50 in the diagnosis of gastric cancer were 17.7, 17.1, 20.4 and 13.8%, respectively, and the positive rate for all four markers combined was 36.6%. Patients with elevated preoperative serum concentrations of CEA, CA 19-9, CA 242 and CA 50, had late clinical tumor stageand significantly poorer overall survival. Five-year survival rates in patients with elevated CEA, CA 19-9, CA 242 and CA 50 were 28.1, 25.8, 27.0 and 24.1%, respectively, compared with 55.0, 55.4, 56.4 and 54.5% in patients with these markers at normal levels (p<0.01). In multivariate Cox proportional hazards analyses, an elevated CA 242 level was determined to be an independent prognostic marker in gastric cancer patients. Combined detection of four tumor markers increased the positive rate for gastric cancer diagnosis. CA 242 showed higher diagnostic value and CA 50 showed lower diagnostic value. In resectable gastric carcinoma, preoperative CA 242 level was associated with disease stage, and was found to be a significant independent prognostic marker in gastric cancer patients.     

术前CEA、CA19-9和CA50的表达水平与结直肠癌临床病理特点的相关性研究--附1 340例病例分析

目的分析手术前血清CEA、CA19-9和CA50在结直肠癌患者中的表达情况,研究其在不同肿瘤临床分期中的表达差异,及其与临床病理学特点的相关性。方法回顾分析2000年1月~2004年9月于肿瘤医院接受治疗的结直肠肿瘤病例1340例,术前采用放射免疫法测定血清CEA、CA19-9和CA50水平,术后综合术前影像学检查、术中探查结果和术后组织病理学检测进行临床分期,应用SPSS12.0统计软件进行相关性分析。结果在1340例患者中,有59例为外院手术后复发或者转移的患者,另外的1281例患者均为初治病例。其中结直肠癌患者1327例。CEA、CA19-9和CA50检测阳性率分别为25.9%、22.3%和22.8%,同手术性质(根治性/姑息性)和脉管侵犯等临床病理指标相关。CEA、CA19-9和CA50在不同肿瘤分期中表达差异显著,主要在D期患者和复发转移患者中出现高阳性率。CEA在粘液腺癌和腺癌组织中表达差异显著。三个指标的表达和患者性别无关。结论CEA、CA19-9及CA50和肿瘤的临床分期密切相关,其阳性表达提示合并淋巴结或者脏器转移可能,是预后不良指标。     

Serial levels of CA 19-9 and CEA in colonic cancer

The use of serial carbohydrate antigen (CA) 19-9 assays was assessed by comparison with serial carcino-embryonic antigen (CEA) levels on the plasmas of 53 patients with colorectal carcinoma. The patients had all undergone resection for their primary tumors and in six instances subsequent resections for hepatic metastases. Initial CA 19-9 levels were greater than or equal to 37 U/mL in 22 of the 53 patients (41%) and in 68% of the patients with metastatic disease. Similar trends of serial CA 19-9 and CEA levels were found in 79% of the 53 patients. One patient with initially normal CEA levels had elevated CA 19-9 levels from the start. In ten of the 53 patients (19%), serial CA 19-9 levels remained low despite tumor recurrence or progression, and despite increasing CEA levels above 5 ng/mL. The increasing serial CEA trends predicted recurrence in 88% and increasing CA 19-9 trends in 50% of cases, which was increased to 70% by including trends of CA 19-9 levels below 37 U/mL. Following hepatic lobectomy, both serial CEA and CA 19-9 levels decreased rapidly. Used alone, serial CA 19-9 levels did not appear to be as sensitive as standard CEA in this retrospective study of selected patients.     

Clinical use of tumor markers in oncology

The perfect tumor marker would be one that was produced solely by a tumor and secreted in measurable amounts into body fluids, it should be present only in the presence of cancer, it should identify cancer before it has spread beyond a localized site (i.e., be useful in screening), its quantitative amount in bodily fluids should reflect the bulk of tumor, and the level of the marker should reflect responses to treatment and progressive disease. Unfortunately, no such marker currently exists, although a number of useful but imperfect markers are available. The predominant contemporary markers are discussed here by chemical class, as follows: glycoprotein markers, including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-hCG), and prostate specific antigen (PSA); mucinous glycopr including CA 15-3, CA 19-9, mucinous-like cancer antigen and associated antigens, and CA 125; enzymes, including prostatic acid phosphatase (PAP), neuron specific enolase (NSE), lactic acid dehydrogenase (LDH), and placental alkaline phosphatase (PLAP); hormones and related endocrine molecules, including calcitonin, thyroglobulin, and catecholamines; and molecules of the immune system, including immunoglobulins and beta-2-microglobulin. The biologic properties of each group of tumor markers are discussed, along with our assessment of their role in clinical medicine today.     

Tissue polypeptide-specific antigen (TPS) in monitoring palliative treatment response of patients with gastrointestinal tumours.

The new proliferation marker, tissue polypeptide-specific antigen (TPS), representing the specific epitope M3 of tissue polypeptide antigen, and three conventional biochemical markers, CEA, CA 19-9 and CA-195, were analysed in 69 patients with advanced gastrointestinal tumours. The aim of our study was to assess the clinical relevance of these markers and to determine whether their use in monitoring the course of the disease can reduce the need for serial imaging procedures. At baseline, pathologically elevated TPS levels occurred in 90% of patients. CEA was elevated in 73%, CA 19-9 in 59% and CA-195 in 68%. With a detection rate of > 90% in both advanced colorectal (n = 37) and pancreatic cancer (n = 20), and of 75% in gastric cancer (n = 12), TPS was the most sensitive marker in all three tumour types included in this analysis. Serial evaluations of TPS and other biochemical markers were available in 39 patients undergoing palliative systemic chemotherapy. Treatment with a fluorouracil-based regimen resulted in a partial response in 5/27 patients with colorectal cancer, whereas 2/12 patients with pancreatic cancer responded to therapy with a high-dose epirubicin combination regimen. All other patients had disease stabilisation or suffered from progressive disease. When compared with the results of serial CT scanning, the TPS correlated best with the course of the disease, the positive predictive value being 75% for a partial response, 96% for stable disease and partial response combined and 100% for progressive disease. The corresponding values for CEA were 50%, 81% and 62% and were similar to those for CA 19-9 and CA-195. In summary, TPS seems to represent a sensitive, clinically relevant and specific marker of proliferative activity in gastrointestinal cancer. According to our preliminary results in colorectal and pancreatic cancer, TPS may be considered as the primary means of monitoring treatment, and imaging reduced to confirm the response.     

Serum tumor markers in colorectal cancer staging,grading, and follow-up

Early diagnosis of colorectal cancer, a frequent neoplasia in industrialized countries, permits curative surgery. In this study we assessed the clinical role of serum tumor markers determination in diagnosing, staging, and grading colorectal cancer; the role of carcinoembryonic antigen (CEA), CA 19-9, tissue polypeptide antigen (TPA) and CA 72-4 in colorectal cancer follow-up was also assessed. In 114 patients with colorectal cancer, the oncofetal antigen CEA was compared with the membrane-associated glycoproteins CA 19-9, CA 242, and CA 72-4 and with the cytokeratins TPA, tissue polypeptide-specific antigen (TPS) and tissue polypeptide monoclonal antigen (TPM). Overall, the most sensitive indices were TPA and TPS (67% and 70%, respectively). Tumor stage influenced the levels of CEA, CA 19-9, and TPA, but not those of TPS, while tumor grade influenced CEA and TPS, but not CA 72-4, TPA, and TPM. TPA was the most sensitive index in identifying early or well-differentiated colorectal cancers. The sensitivity was enhanced when this marker was determined in combination with CEA, in diagnosing both advanced and early colorectal tumors. Seventy-seven patients were followed up after therapy for at least 18 months. CEA was the most sensitive index of recurrence (58%); however, this sensitivity is too low to consider tumor markers useful in colorectal cancer follow-up. © 1996 Wiley-Liss, Inc.     

Comparison of the tumor markers CEA, TPA, and CA 19-9 in colorectal carcinoma

In 103 patients with colorectal carcinoma carcinogenic antigen, 19-9 (CEA), tissue polypeptide (TPA) and carbohydrate antigen (CA 19-9) were measured in serum. The values determined in these patients and in a control group have been converted into specificity-sensitivity diagrams. Comparison of diagrams of the three markers showed that CEA has the greatest sensitivity in colorectal carcinoma. Different ways to enhance the sensitivity by combination of the markers have been tried. By combination, however, the sensitivity of the single markers is not essentially enhanced.     

Hydrophobicity and lectin affinity of alkaline phosphatase isozymes in seminoma and normal testis

Isozymes of alkaline phosphatases (ALP) in seminoma and normal testis were separated by use of high-performance liquid chromatography and a TSK-gel phenyl-5PW column. The tissue-nonspecific (liver) ALP (LAP) was the dominating isozyme, consisting of more than 90% ALP activity. The placental ALP (PLAP)-like enzyme contributed to 4-8% of the total ALP activity. The intestinal isozyme (IAP) could not be identified. The glycosylation patterns of the isozymes were studied using concanavalin A (Con A) affinity chromatography and batch elution with competing sugar. All PLAP activity in placental extracts and LAP activity in liver extracts was bound to Con A-Sepharose. In the tumor extracts, only 50-70% of the PLAP-like enzyme and 20-50% of the LAP activity from seminomas were bound to Con A-Sepharose. A similar binding pattern of the PLAP-like enzyme and LAP was also seen in the normal testes. This variability in Con A reactivity with PLAP or the PLAP-like enzyme was also reflected in serum of seminoma patients and of pregnant women. Thus, ALP expressed in seminoma has different lectin affinity characteristics compared with the same isozyme from placenta and liver, but almost identical to ALP in the normal testes. These findings imply that the PLAP-like enzyme and LAP in the testis can be discriminated from PLAP of placenta and LAP of liver by carbohydrate lectin affinity. It also supports the concept that the increased amounts of ALP in seminomas result from the enhanced eutopic expression of enzymes normally expressed in the testis.