糖类抗原125、糖类抗原15-3、糖类抗原19-9和人附睾蛋白4单独及联合检测对卵巢癌的诊断价值

目的研究糖类抗原125(CA125)、CA15-3、CA19-9和人附睾蛋白4(HE4)单独及联合检测对卵巢癌的诊断价值,探讨最优的联合诊断方案。方法选取90例卵巢癌患者、90例良性卵巢疾病患者及90同期健康体检者,分别作为肿瘤组、良性组和健康组。比较3组受试者血清CA125、CA15-3、CA19-9和HE4水平及阳性率,比较上述四种肿瘤标志物单独及联合检测对卵巢癌的诊断灵敏度、特异度及准确度。结果肿瘤组患者CA125、CA15-3、CA19-9和HE4水平及阳性率均高于良性组患者和健康组受试者,良性组患者血清CA125、CA15-3和CA19-9水平均高于健康组受试者,良性组患者血清CA125、CA15-3、CA19-9和HE4阳性率均高于健康组受试者,差异均有统计学意义(P﹤0.05)。CA125+CA15-3+HE4、CA125+CA15-3+CA19-9+HE4诊断卵巢癌灵敏度最高,均为91.11%。HE4单独诊断卵巢癌的特异度最高,为94.44%。CA125+CA15-3+HE4诊断卵巢癌的准确度最高,为85.93%。结论CA125+CA15-3+HE4三项联合检测可提高卵巢癌诊断效率,对临床诊断卵巢癌有参考价值。     

Long-term prognostic study of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA 15-3) in breast cancer

Background  Tumor markers are frequently used for screening and monitoring in oncology. We investigated the use of preoperative tumor marker (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA] 15-3) levels in estimating the prognosis of breast cancer patients. Methods  We conducted a retrospective study in patients who underwent breast cancer surgery at National Cancer Center Hospital between 1975 and 1994 and whose serum CEA (n = 1663) and CA 15-3 (n = 1500) levels were measured prior to operation. When we excluded patients with stage IV disease from the study, the CEA level was within the normal range in 1470 patients, while 150 patients had an elevated CEA level. For CA 15-3, 1395 patients were within the normal range, while 70 patients exhibited an elevated level. Results  The 5-year and 10-year survival rates for patients with normal CEA levels were 87% and 76%, respectively. However, the 5-year and 10-year survival rates for patients with elevated CEA levels were 76% and 65%, respectively. At both time points, patients with normal CEA levels had higher survival rates (P < 0.05). The 5-year and 10-year survival rates for the patients with normal CA 15-3 levels were 86% and 76%, respectively, while only 71% and 52% patients with elevated CA 15-3 levels survived at 5 and 10 years, respectively. These differences were also significant (P < 0.05). However, there were no significant differences in disease-free survival (DFS) according to CEA or CA 15-3 levels. Conclusion  There was a positive correlation between CEA levels and CA 15-3 levels and patient prognosis. Thus, the levels of these tumor markers may help to determine prognosis in breast cancer patients.     

Carbohydrate antigen 242 highly consists with carbohydrate antigen 19-9 in diagnosis and prognosis of colorectal cancer: study on 185 cases

The objective of the study was to compare the clinical value of preoperative serum carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 242 (CA242) in diagnosis and prognosis for 5-year recurrence-free survival (RFS) in patients with colorectal cancer (CRC). Preoperative serum CA19-9 and CA242 concentrations were detected by C12 protein chip diagnostic system in 185 patients with CRC, and informative data were collected during 5-year follow-up periods. The value of CA19-9 and CA242 in diagnosis and prognosis for 5-year RFS as well as their consistencies and correlations were comparatively analyzed. The sensitivities of CA19-9 and CA242 were only 19.5 and 20%, respectively; the efficiencies of two TMs were 53.9 and 54.2%, respectively; and two TMs increased significantly with advancing clinical stages (P < 0.0001). Preoperative CA19-9 and CA242 levels correlated with stage (r, 0.411 and 0.408) and CEA concentration (r, 0.553 and 0.630). The concentrations of two TMs closely correlated with each other (r = 0.829), and two TMs had a very strong consistency in diagnosis (κ = 0.931). Among 88 of 185 cases with complete follow-up information on RFS, patients with positive preoperative serum CA19-9 or CA242 had higher 5-year recurrent rates (72.2% vs. 44.3%, P = 0.034; 76.5% vs. 43.7%, P = 0.015) and reduced median RFS (14 vs. 36 months, 12 vs. 36 months) compared with those with negative TMs. The consistency of predicting prognosis for RFS of two TMs was extremely strong (κ = 0.964). ROC curves analysis showed that CA242 test performed better than CA19-9 test (AUC, 0.648 vs. 0.605). Univariate analysis showed that preoperative serum status of both TMs was correlated with 5-year RFS (P < 0.05), whereas multivariate Cox regression model analysis revealed that none of them were independent prognostic factors for RFS. Both CA19-9 and CA242 had strong consistencies in diagnosis and prognosis for predicting 5-year RFS. CA242 demonstrated superior value to CA19-9 in CRC.     

Circulating CA 15-3 antigen levels in non-mammary malignancies

Abnormal CA 15-3 antigen levels are found in the serum of most patients with advanced breast carcinoma. Elevations of this marker are less frequently seen in other malignancies. Circulating CA 15-3 levels might be useful in the differential diagnosis of the primary site of cancer. We studied the levels of CA 15-3 in 500 patients with different non-mammary cancers. Elevations of CA 15-3 (greater than 40 U ml-1) were observed in all types of epithelial malignancies, especially in ovarian (46%), respiratory (26%) and liver (30%) carcinomas. Abnormal values were observed in some patients with haematological malignancies and sarcomas, but not in melanoma or neurological tumours. CA 15-3 antigen levels correlated with the extent of non-mammary malignant tumours. Patients with locoregional cancer had a significantly smaller proportion of elevations of the antigen than those with distant metastases (12% versus 35%, P less than 0.001). In particular, elevated CA 15-3 levels were observed in 70% of patients with metastatic ovarian cancer. Liver involvement by cancer did not produce more elevations of CA 15-3 than metastases to other organs (32% versus 39%). Simultaneous determination of circulating CA 15-3 and CA 125 antigens in 58 patients with cancer of the ovary showed that CA 15-3 is elevated in some cases of ovarian carcinoma with non-elevated CA 125, and that CA 15-3 and CA 125 are distinct antigens. We conclude that circulating CA 15-3 antigen levels can be found elevated in virtually all types of cancer, particularly when distant metastases are present. Therefore, CA 15-3 levels should not be used in the differential diagnosis of the primary site in patients with metastatic malignancies of unknown origin. Evaluation of CA 15-3 levels may enhance the sensitivity of CA 125 in monitoring the course of ovarian carcinoma.     

血清癌胚抗原联合糖类抗原19-9检测对胰腺癌筛查的临床价值评估

目的 研究血清癌胚抗原(CEA)联合糖类抗原19-9(CA19-9)检测对胰腺癌筛查的临床价值.方法 将103例胰腺癌患者作为胰腺癌组,选取同期收治的105例胰腺炎患者以及健康体检的97例健康人群作为胰腺炎组及健康对照组.对比治疗前3组血清CEA、CA19-9水平,以及手术前后胰腺癌患者血清CEA、CA19-9水平;对...     

Monoclonal antibodies recognizing tumor-associated antigen of human ovarian mucinous cystadenocarcinomas

Spleen cells from BALB/c mice immunized with human ovarian cystadenocarcinoma extract were fused with the mouse myeloma cell line P3/NSI/1-Ag 4 in the presence of polyethylene glycol (Mr 4000). Of the 46 hybrids obtained, four secreted antibodies preferentially reactive to the immunizing ovarian tumor extract. Two of these hybrids, which showed no reaction with normal controls, were selected for cloning by the limiting dilution method. The numerous clones obtained from each hybrid were screened against a panel of five ovarian tumor extracts, pooled normal ovary extracts, and pooled normal human sera. One clone from each hybrid that showed specificity for ovarian mucinous cystadenocarcinomas was recloned to assure monoclonality and to establish a permanent hybridoma cell line. The antibodies secreted by these cell lines were of IgG1 subclass with kappa light chains. These antibody-producing hybridomas were selected for further analysis of the antibody specificity by a solid-phase radioimmunoassay and quantitative absorption tests. The monoclonal antibodies recognized an antigenic determinant present only in mucinous cystadenocarcinomas of the ovary. These did not react with any other gynecological or nongynecological tumor thus far tested. The antigen was not demonstrable in any normal adult tissues tested. Among fetal tissues examined, only fetal intestine extract showed a positive reaction. The antigenic determinant recognized by these monoclonal antibodies was unrelated to carcinoembryonic antigen, normal glycoprotein, normal human serum components, or human ABO blood group materials. These antibodies, which have relatively high affinity and can be produced in large amounts, will be useful for the isolation and immunochemical characterization of this antigen. The purified antigen and the specific antibodies could be then combined in a sensitive radioimmunoassay for the early detection of the antigen in the sera and body fluids of patients with ovarian mucinous cystadenocarcinomas.     

Expression of carbohydrate antigen 19-9 and stage-specific embryonic antigen 1 in nontumorous and tumorous epithelia of the human colon and rectum

The expression of carbohydrate antigen 19-9 (CA 19-9) and stage-specific embryonic antigen 1 (SSEA-1) in various human colorectal epithelia was examined by an immunohistochemical method. In mucosa remote from the carcinoma, CA 19-9 was not expressed, whereas SSEA-1 was only faintly expressed in lower crypts in all cases. In mucosa adjacent to the carcinoma, CA 19-9 was weakly expressed in upper crypts in 20% of the cases, whereas SSEA-1 was expressed not only in lower crypts in all cases but also in upper crypts in 93.3% of the cases. In adenoma, CA 19-9 was expressed in 80.6% of the cases, and SSEA-1 was expressed in all cases. The expression of both antigens was to some extent related to the degree of cellular atypia. In focal carcinoma in adenoma, CA 19-9 was strongly and diffusely expressed in 50% of the cases, and SSEA-1 was strongly and diffusely expressed in all cases. In advanced carcinoma, CA 19-9 was homogeneously or heterogeneously expressed in 82.2% of the cases, and SSEA-1 was homogeneously or heterogeneously expressed in all cases, but lower intensity of SSEA-1 staining was associated with a decrease in the degree of carcinoma differentiation. These results show that the expression of both CA 19-9 and SSEA-1 changes along with neoplastic transformation and progression in the colon and rectum. Immunohistochemical studies of SSEA-1 in flat colorectal mucosa might be a useful approach for detecting foci with preneoplastic change in the general population, whereas those of SSEA-1 and CA 19-9 could be a useful method for detecting focal carcinoma in adenoma.     

超声联合血清糖类抗原125、糖类抗原19-9诊断卵巢癌的临床价值

目的 探究超声联合血清糖类抗原125(CA125)、糖类抗原19-9(CA19-9)对卵巢癌的临床诊断价值.方法 选取卵巢癌患者47例作为观察组,同期卵巢良性疾病患者60例作为对照组.两组患者术前均实施超声检查和血清CA125、CA19-9检测.统计两组患者超声评分、血流阻力指数(RI)、血清CA125和CA19-9水平,对比不同分期观察组患者超声评分、RI、血清CA125和CA19-9水平,并对超声、血清CA125、血清CA19-9单独及联合检测对卵巢癌的诊断价值进行分析.结果 观察组患者超声评分、血清CA125和CA19-9水平均明显高于对照组,RI明显低于对照组,差异均有统计学意义(P﹤0.01).Ⅰ、Ⅱ期卵巢癌患者超声评分、血清CA125和CA19-9水平均明显低于Ⅲ、Ⅳ期患者,RI明显高于Ⅲ、Ⅳ期患者,差异均有统计学意义(P﹤0.01).受试者工作特征(ROC)曲线分析结果显示,超声检查、血清CA125、血清CA19-9联合检测对卵巢癌的曲线下面积高于各项指标单一检测(P﹤0.01).结论 超声、血清CA125、CA19-9三者联合能将各自优势相互结合,有效提高卵巢癌的诊断价值.     

TPS in breast cancer--a comparative study with carcinoembryonic antigen and CA 15-3.

The serum levels of tissue polypeptide antigen were determined using the M3 monoclonal antibody (TPS) and compared with the serum levels of carcinoembryonic antigen (CEA) and breast carcinoma antigen 15-3 (CA 15-3) in 96 patients with benign breast tumors, in 25 breast cancer patients with no evidence of disease, in 139 preoperative breast cancer patients and in 298 samples of 25 breast cancer patients during therapy monitoring (4-22 samples per patient). The 95th percentile of TPS in 89 apparently healthy females was 51 U/l. The 95th percentile of TPS in patients with benign breast tumors was 55 U/l. The maximum TPS level in breast cancer patients with no evidence of disease was 56 U/l. In preoperative breast cancer the number of patients with TPS levels above the 95th percentile of TPS in benign breast tumors was significantly higher in stage III breast cancer as compared with stage I+II. This was not established for CEA and CA 15-3. During therapy monitoring TPS followed the course of the disease faster than CEA and CA 15-3 in patients with bone metastases, liver metastases, lung metastases and pleural effusion, with one exception. TPS levels could be correlated with progression of disease in patients with normal and steady levels of CEA and/or CA 15-3.     

Cancer antigen 125, carcinoembryonic antigen, and carbohydrate determinant 19-9 in ovarian tumors

The authors studied data of combination assays of tumor markers, because simultaneous elevation of different types of tumor markers in the serum was puzzling. They interpreted such phenomena regarding cancer antigen 125, carcinoembryonic antigen, and carbohydrate determinant 19-9 in ovarian tumors. The tissue expression of the antigens was compared with preoperative serum levels. Several different factors were found to cause the simultaneous elevation of two or three of these markers in the serum. Furthermore, even when the levels of some of the tumor markers were raised in the serum, the ovarian tumor did not always produce the marker by itself. This study indicates that immunohistochemical identification of a marker in tumor tissue is prerequisite to the use of that marker in the serum to monitor disease status.     

Diagnostic value of preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 in colorectal cancer

Background

Since the first introduction of tumour markers, their usefulness for diagnosis has been a challenging question. The aim of the present prospective study was to investigate, in colorectal cancer patients, the relationship between preoperative tumour marker concentrations and various clinical variables.

Methods

The study prospectively enrolled 131 consecutive patients with a confirmed diagnosis of colorectal carcinoma and 131 age- and sex-matched control subjects with no malignancy. The relationships of the tumour markers carcinoembryonic antigen (cea) and carbohydrate antigen (ca) 19-9 with disease stage, tumour differentiation (grade), mucus production, liver function tests, T stage, N stage, M stage were investigated.

Results

Serum concentrations of cea were significantly higher in the patient group than in the control group (p = 0.001); they were also significantly higher in stage iii (p = 0.018) and iv disease (p = 0.001) than in stage i. Serum concentrations of cea were significantly elevated in the presence of spread to lymph nodes (p = 0.005) in the patient group. Levels of both tumour markers were significantly elevated in the presence of distant metastasis in the patient group (p = 0.005 for cea; p = 0.004 for ca 19-9).

Conclusions

Preoperative levels of cea and ca 19-9 might provide an estimate of lymph node invasion and distant metastasis in colorectal cancer patients.     

血清miiRNA-196a联合糖类抗原125、糖类抗原19-9对宫颈癌的诊断价值

目的 探讨血清miRNA-196a联合糖类抗原19-9(CA19-9)及CA125诊断宫颈癌的临床价值.方法 选取180例宫颈癌患者(宫颈癌组)、50例宫颈良性肿瘤患者(良性组)及50例健康体检者(对照组)为研究对象,比较不同临床分期宫颈癌患者血清miRNA-196a、CA125、CA19-9水平,比较3组研究对象血清...     

Carbohydrate antigen expression in colorectal cancer

Several major alterations in glycosylation of glycoproteins and glycolipids occur in colorectal cancer resulting in the expression of cancer associated antigenic epitopes. These changes can occur either in the outer peripheral, middle, or inner core regions of the carbohydrate side chains. The major changes are increased expression, inappropriate expression, deletion and modification of antigenic structures present in normal colorectal tissues. These changes are illustrated by recent studies on the expression of several blood group antigens such as A,B,H, and Leb antigens, modified blood group related antigens such as sialosyl Lea, CA 50, SPan-1, Lex (X) and Ley (Y) antigens and inner core carbohydrate antigen such as T, Tn and Sialosyl-Tn antigens. These changes also occur in adenomatous polyps and appear to correlate with parameters of malignant potential. Thus, these carbohydrate antigens may serve as premalignant markers which may be useful in identification and screening of subjects at high risk for developing colorectal cancer. Carbohydrate containing cancer and malignant markers show considerable promise as potential candidates in immunodetection, staging and therapy of colorectal cancer.     

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.     

Establishment and characterization of a human pancreatic cancer cell line (SUIT-2) producing carcinoembryonic antigen and carbohydrate antigen 19-9

A new tumor cell line (SUIT-2) derived from a metastatic liver tumor of human pancreatic carcinoma has been established in tissue culture and in nude mice, and maintained for over five years. In tissue culture, the cells grew in a monolayered sheet with a population doubling time of about 38.2 hr, and floated or piled up to form small buds above the monolayered surface in relatively confluent cultures. Chromosome counts ranged from 34 to 176 with a modal number of 45. Subcutaneous injection of cultured cells into nude mice resulted in tumor formation, histopathologically closely resembling the original neoplasm which had been classified as moderately differentiated tubular adenocarcinoma. Electron microscopic observation of the neoplastic cells revealed a characteristic pancreatic ductal epithelium. SUIT-2 cell line produces and releases at least two tumor markers, carcinoembryonic antigen and carbohydrate antigen 19-9, propagates even in serum-free medium, and metastasizes to the regional lymph nodes in nude mice xenografts.     

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.     

Detection of ovarian cancer marker CA 125 in human seminal plasma

Ovarian cancer marker CA 125-like immunoreactivity was detected in human seminal plasma. The levels were 17-720 U/ml in specimens from normospermic men (n = 35), 22-1150 U/ml in samples from 46 men with either oligo-, astheno-, terato- or necrospermia, and 36-1096 U/ml in 7 vasectomized men. No significant differences were found in the CA 125 levels between the groups studied. Low CA 125 levels (less than 35 U/ml) were detected in male sera. Serial dilutions of seminal plasma and ovarian cancer serum gave parallel dose-response curves. No correlation was observed between the age of men, sperm count, volume of seminal plasma or percent of motile spermatozooa and CA 125 levels in seminal plasma. CA 125 in seminal plasma does not seem to be of testicular origin, as the levels in vasectomized and non-vasectomized men were similar. In gel filtration, CA 125 immunoreactivity in seminal plasma and ovarian cancer serum eluted in the same volume corresponding to a molecular weight of about 130 kD.     

Comparison of circulating CA15-3 and carcinoembryonic antigen levels in patients with breast cancer

An immunoradiometric assay (IRMA) has been used to determine circulating levels of the breast cancer-associated antigen, CA15-3. Of 1,050 normal control subjects, serum from 99 (9.4%) had CA15-3 antigen levels greater than 22 U/mL, while that from 58 (5.5%) and 14 (1.3%) had levels greater than 25 U/mL and 30 U/mL, respectively. In contrast, 115 of 158 patients (73%) with metastatic breast cancer had CA15-3 levels greater than 22 U/mL. Thirteen of 26 patients (50%) with only local metastases, 27 of 34 (79%) of those with only bone metastases, and 20 of 24 (83%) with hepatic metastases had CA15-3 levels greater than 22 U/mL. Furthermore, nine of 31 patients (29%) with primary breast cancer had CA15-3 levels greater than 22 U/mL. CA15-3 and carcinoembryonic antigen (CEA) levels were compared for the same patient population. Significantly more patients with metastatic breast cancer had elevated CA15-3 levels than had elevated CEA levels (P less than .001). Furthermore, the CA15-3 IRMA was more sensitive than the CEA assay in patients with only bone metastases, as well as those with only local metastases. Significantly more patients with primary carcinoma of the breast also had elevated CA15-3 than had elevated CEA levels (P less than .02). CA15-3 levels were greater than 22 U/mL in patients with nonmalignant conditions, including five of 25 patients (20%) with benign breast diseases, and 23 of 52 patients (44%) with benign liver diseases. Furthermore, CA15-3 levels were also greater than 22 U/mL in 24 of 54 patients (44%) with gastrointestinal (GI) malignancies, 12 of 17 patients (71%) with bronchogenic carcinoma, and 29 of 44 patients (66%) with epithelial ovarian carcinoma. Serial CA15-3 levels correlated with clinical disease course. Nineteen of 21 patients (91%) with tumor progression had at least a 25% increase in CA15-3 levels. Conversely, seven of nine patients (78%) with tumor regression had at least a 50% decrease in CA15-3 levels. Among 27 patients with stable disease, 16 (59%) had levels that did not vary by more than +/- 25% of the original CA15-3 levels. These results indicate that the CA15-3 antigen is a sensitive marker for the evaluation and monitoring of patients with breast cancer.