Diagnostic value of carcinoembryonic antigen and carcinoma antigen 19-9 for colorectal carcinoma

Objective: The purpose of this study was to evaluate the diagnostic efficiency of colorectal carcinoma (CRC) with the tumor markers Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 19-9 (CA 19-9), in addition to investigating whether CA 19-9 can be used to screen the disease process in patients with CRC who had no elevation of CEA levels. Methods: Serum levels of CEA and CA 19-9 were measured in: 138 patients with CRC; 111 patients with benign colorectal diseases. The diagnostic value was performed using the logistic regression equation and receiver operating characteristic curves (ROC). Results: The serum levels of CEA and CA 19-9 in the patients with CRC were significantly higher than those in the patients with benign colorectal diseases (P < 0.001). Receiver operating characteristic curves (ROC) in the patients with CRC versus those with benign colorectal disease yielded the optimal cut-off value of 3.36 ng/ml for CEA and 23.9 U/ml for CA 19-9, respectively. The area under ROC curve (AUC) was 0.789 for CEA, 0.690 for CA 19-9 and 0.900 for the combination of the two tumor markers. The combination resulted in a higher Youden index and a sensitivity of 85.3%. Conclusion: The combined detection of serum CEA and CA 19-9 could play a pivotal role in the diagnosis of CRC, and could drastically improve the sensitivity for the diagnosis of CRC. CA 19-9 might be a tumor biomarker in addition to CEA for CRC.     

mRNA markers of breast cancer nodal metastases: comparison between mammaglobin and carcinoembryonic antigen in 248 patients

Histological detection of axillary lymph node metastases is still the most valuable prognostic parameter for breast cancer, but about 30% of node-negative patients relapse within five years, suggesting that current methods are inadequate for identifying metastatic disease. More sensitive, PCR-based methods for the detection of metastatic cells are now available, enabling the amplification of cancer cell-specific mRNA messages by the RT-PCR assay. An ideal tumour marker, consistently expressed in tumour samples and not at all in normal lymph nodes, remains to be identified. The present study first investigated the expression of seven mRNA markers, CEA, CK19, c-Met, mammaglobin, MUC-1, beta1-->GalNAc-T and p97, selected on the basis of their previously reported specificity for breast cancer cells. Eighteen lymph nodes were examined from patients without tumours. Only mammaglobin mRNA and CEA mRNA were not expressed in normal nodes. All of the other markers showed a band of expression in 17%-55% of cases, indicating that they are not breast cancer-specific. CEA mRNA and mammaglobin mRNA expression could be detected in 15/20 (75%) and 19/20 (95%) primary breast carcinomas, respectively. The expression of mammaglobin mRNA and CEA mRNA was then compared in axillary lymph nodes from 248 consecutive breast cancer patients, 89 with histologically documented lymph node metastasis and 159 without histological evidence of metastatic disease. Ninety-seven per cent of the patients with histologically involved nodes showed expression of mammaglobin mRNA, whereas CEA mRNA was expressed in 79% of these cases. In the group of patients with histologically negative lymph nodes, 46 (29%) and 32 (20%) were found to be positive for mammaglobin and CEA expression, respectively, indicating the presence of metastases not detected by routine histological examination of one lymph node section. These results show that both mammaglobin RT-PCR and CEA RT-PCR are useful tools for the detection of breast cancer metastases in axillary lymph nodes. The detection sensitivity of the mammaglobin RT-PCR is far superior to that of the CEA RT-PCR, allowing the diagnosis of occult metastases in nearly one-third of cases.     

Systemic inflammatory markers and serum lactate dehydrogenase predict survival in patients with Wilms tumour

IntroductionMarkers of inflammation such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been found to be associated with survival in cancer patients. The aim of the current study was to establish the prognostic significance of simple laboratory markers of systemic inflammation in paediatric patients diagnosed with Wilms tumour (WT). Additionally, we aimed to compare the complete blood count (CBC) parameters of WT patients and the non-oncological control group.Material and methodsThe study group included 88 children diagnosed with WT. Clinicopathological data, as well as CBC, C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels at diagnosis, were obtained. Additionally, the laboratory results of 62 healthy control paediatric patients were collected. Uni- and multivariate proportional Cox’s hazard analyses were computed to create a model predicting relapse-free survival (RFS) and overall survival (OS) in the study group.ResultsHigh CRP, LDH, and NLR were associated with a higher stage of WT and shorter RFS, whereas all parameters correlated with OS. In multivariate analysis, only LDH levels had adverse significance in predicting RFS. C-reactive protein and LMR retained their prognostic value in the multivariate model predicting OS. Comparing the WT group with controls, high LDH, high CRP, high NLR, and high PLR were associated with WT presence.ConclusionsPreoperative LDH, CRP, NLR, PLR, and LMR have significant prognostic value in patients with WT independently of age and stage. Combined low CRP and high LMR identified the group of patients with excellent OS. Patients with high LDH were characterized by the highest risk of relapse.     

Examination of enzyme-altered foci with gamma-glutamyl transpeptidase, aldehyde dehydrogenase, glucose-6-phosphate dehydrogenase, and other markers in methacrylate-embedded liver

F344 Male rats weighting between 90 and 110 gm were given 90 ppm diethylnitrosamine in their drinking water for 5 weeks. Seven weeks after the administration of carcinogen was completed, the rats were sacrificed and sections of their livers were embedded in methacrylate. Serial sections 2 or 4 micron in thickness demonstrated the presence of gamma-glutamyl transpeptidase, acid phosphatase, adenosine triphosphatase, aldehyde dehydrogenase, alkaline phosphatase, alpha-naphthyl butyrate esterase, DT diaphorase, glucose-6-phosphate dehydrogenase, and 5'-nucleotidase activity and glycogen. The use of 4-micron sections of methacrylate-embedded tissue allows the evaluation of many more phenotypic markers in serial sections than is currently possible with frozen sections.     

血浆胃泌素释放肽前体，细胞角蛋白19和癌胚抗原对各型肺肿瘤的诊断价值

目的探讨胃泌素释放肽前体（ProGRP）,细胞角蛋白19（CYFRA21—1）,癌胚抗原（CEA）对各型肺癌的诊断价值。方法检测85例健康对照人群、49例肺良性疾病患者及143例各型肺癌患者血浆中的ProGRP,CYFRA21-1,CEA三个指标,并对小细胞肺癌（SCLC）患者进行ProGRP的跟踪监测。结果SCLC患者中ProGRP水平[中位数（M）179．1ng／m1）]明显高于肺腺癌（M35．3ng／m1）、鳞癌（肘33．3ng／m1）、健康对照（膨35．6ng／m1）和良性肺病（M33．3ng／m）,差异有统计学意义（P〈0．001）;ProGRP对SCLC的诊断灵敏度和特异性分别为60．6％和95．0％。SCLC治疗有效组,ProGRP降低了45．9％,SCLC疾病进展组,ProGRP升高了103．1％,差异均有统计学意义（P〈0．05）。CEA在肺腺癌转移组中水平（M10．22ng／ml）明显高于无转移组（M3．85ng／m1）和鳞癌组（M2．56ng／m1）,差异有统计学意义（P〈0．01）。结论血浆ProGRP是一个很好的SCLC诊断指标和疗效评价指标;CEA明显升高是腺癌肺外转移指标。     

Epithelial markers in prostatic, bladder, and colorectal cancer: an immunoperoxidase study of epithelial membrane antigen, carcinoembryonic antigen, and prostatic acid phosphatase

Twenty prostatic adenocarcinomas, 20 transitional cell carcinomas of the bladder, and 20 colorectal adenocarcinomas were stained for epithelial membrane antigen, carcinoembryonic antigen, and prostatic acid phosphatase. Polyclonal affinity purified first and second antibodies and an indirect immunoperoxidase technique were used. All of the colorectal and bladder tumours and 16/20 prostatic tumours were positive for epithelial membrane antigen. All 20 colorectal, 7/20 bladder, and 5/20 prostatic tumours stained for carcinoembryonic antigen. All of the prostatic adenocarcinomas and none of the colorectal or bladder tumours were positive for prostatic acid phosphatase. These markers may be used to discriminate between tumours arising from these sites.     

血清CEA水平在EGFR-TKI治疗非小细胞肺癌的应用价值

目的：探讨血清癌胚抗原(carcino-embryonic antigen,CEA)在表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗非小细胞肺癌的价值。方法：回顾性收集确诊非小细胞肺癌并使用EGFR-TKI治疗患者的治疗前后CEA水平、一般资料、病理亚型、分期、分子标记物和CEA对治疗决策的影响,并定期影像学评价,随访至进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。通过Kaplan-Meier绘制生存曲线,log-rank检验比较不同CEA组间的生存差异, Cox回归分析预后因子。结果：本研究纳入2002年6月至2011年8月广东省肺癌研究所使用EGFR-TKI的非小细胞肺癌患者209例。分为3组：L组(CEA≤5,n=54),M组(520,n=103)。L组、M组和H组的中位PFS分别为19、17和13月(95% CI,14.61~19.39;P=0.018);中位OS分别为32、31和24月(95% CI,25.14~30.86;P=0.010)。治疗前低CEA的患者有显著延长的PFS和OS。CEA升高同时伴有影像学进展的45例,CEA升高无影像学进展证据的27例,两组的中位PFS分别为13月和14月(95% CI,10.51~15.49,P=0.195);中位OS分别为23月和28月(95% CI,19.81~30.19,P=0.156)。CEA升高无影像学进展的27例患者均随访至进展才改变治疗策略,中位无进展时间为24.3月(3~111月)。结论：治疗前血清CEA水平和EGFR-TKI治疗晚期非小细胞肺癌的预后呈负相关;治疗过程中CEA升高时,需结合影像学和症状来决定是否改变治疗策略。     

Expression of carcinoembryonic antigen, T-antigen, and oncogene products as markers of neoplastic and preneoplastic colonic mucosa

Several crypt abnormalities have been demonstrated in the mucosa of neoplastic and preneoplastic lesions of the large intestine. In addition, certain tumor markers are expressed in large intestinal carcinoma but not in normal mucosa. To determine whether any correlation exists between tumor marker expression and crypt abnormalities and at what stage markers are expressed, we studied specimens of large intestinal mucosa from 13 patients with preneoplastic conditions (adenomatous polyp, familial polyposis, Crohn's disease, and ulcerative colitis). The tumor markers examined include carcinoembryonic antigen (CEA), the ras gene products p21 and p21ser (mutated form), and beta-D-galactosyl-(1----3)-alpha-N-acetyl-D-galactosamine (gal--gal NAc, also known as T-antigen). Results were compared to those of five cases of adenocarcinoma of colon and three control cases of colonic mucosa obtained at immediate autopsy. All four markers were expressed in three of the five cases of adenocarcinoma, but none were expressed in the control cases. Variable expression of each marker was demonstrated in the dilated, distorted crypts of preneoplastic lesions. CEA and gal--gal NAc appeared to be expressed most frequently, suggesting that these are common markers or are expressed at an earlier stage in the neoplastic process than p21 or p21ser. Demonstration of such markers in preneoplastic conditions may be of use in determining the malignant potential and in monitoring these lesions.     

Diagnostic and prognostic significance of serum cholinesterase and lactate dehydrogenase in breast cancer.

Serum cholinesterase (ChE) and Lactate dehydrogenase (LDH) activities were estimated in 40 cases of carcinoma breast, 25 cases of benign tumours and compared with healthy controls (30 cases). Significant difference in enzyme activities were obtained between benign and malignant neoplasms of the breast when compared with each other as well as when compared with healthy controls. Also, there were significant enzyme changes between non-metastatic cases and those with metastasis and when Stage I and Stage II cancers were compared with those in Stage III and Stage IV. No difference in enzyme levels were recorded between pre and post-operative cases and in different types of breast cancers. While ChE was depressed in 80 per cent cases of malignancy breast, serum LDH was raised in 73.3 per cent cases.     

Diagnostic efficiency of carcinoembryonic antigen and CA125 in the cytological evaluation of effusions.

In our previous study, the combination of the concentrations of carcinoembryonic antigen (CEA) and CA125 and the findings from cytological examination in 189 benign and malignant pleural and peritoneal effusions was useful in the diagnosis/classification of malignant effusions. Sensitivity of CEA (level, greater than 5 ng/mL) was 68%; specificity was 99% for the diagnosis of malignant effusions secondary to carcinoma of the lung, breast, gastrointestinal tract, and mucinous carcinoma of the ovary. Sensitivity of CA125 (level, greater than 5000 U/mL) was 85%; specificity was 96% for the diagnosis of malignant effusions in carcinoma of the ovary, fallopian tube, and endometrium. We now expanded the study to include 840 pleural and peritoneal effusions (benign, n = 520; malignant, n = 320) and analyzed the data by the statistical method of Rudolph and colleagues. Based on new cutoff values, ie, CEA level at 6.3 ng/mL and CA125 level at 3652 U/mL, the sensitivities for detection of malignant effusions secondary to carcinomas of the lung, breast, and gastrointestinal tract and mucinous carcinoma of the ovary varied between 75% and 100%; specificity was 98%. Sensitivity of CA125 for detection of malignant effusions from müllerian epithelial carcinoma was 71%; specificity was 99%. The elevated CEA fluid level alone helped to diagnose malignant effusions of the gastrointestinal tract in 54%, breast in 19%, and lung in 16%. The high CA125 fluid level was predictive of müllerian epithelial carcinoma. Adjunctive use of CEA and CA125 levels in fluid enhances the sensitivity of cytological diagnosis and may be predictive of the primary site in patients who present with carcinoma of an unknown primary source.     

Detection of tumor markers including carcinoembryonic antigen, APC, and cyclin D2 in fine-needle aspiration fluid of breast

Context.-The traditional triple test for breast cancer diagnosis is physical examination, mammography, and aspiration cytology. However, the accuracy of mammography on young women with nonatrophied breasts is poor compared with that for women older than 50 years, and additional methods for diagnosis of breast cancer are needed.Objective.-To investigate whether carcinoembryonic antigen (CEA), CA 15-3, and CA 125 concentrations in breast aspiration fluid are useful as breast cancer biochemical markers and whether APC and cyclin D2 gene promoter hypermethylation could be regarded as a breast cancer molecular marker.Design.-CEA, CA 15-3, and CA 125 concentrations were measured, and methylation status of the APC gene promoter 1A and the promoter region of the cyclin D2 gene were analyzed using a methylation-specific polymerase chain reaction assay of ex vivo breast aspiration fluid obtained from 49 samples of excised breast tissue.Setting.-The specimens were collected during a 1-year period in the tertiary care teaching hospital in Seoul, Korea.Patients.-Forty-nine patients with breast masses were surgically treated. Thirty-four patients had breast cancer, and 15 had benign breast disease.Results.-Aspiration fluid CEA concentrations were significantly higher in breast cancer cases than in cases of benign breast disease (mean, 69.90 ng/mg protein vs 0.68 ng/mg protein, respectively; P < .001). At 90% specificity of the assay (CEA, 2.13 ng/mg protein), the corresponding sensitivity for breast cancer detection was 62%, according to the receiver operating characteristic curve drawn. The APC gene promoter 1A and the promoter region of the cyclin D2 gene were methylated in 42% (14/33) and 70% (23/33) of the breast cancer aspiration fluid samples, respectively. A cumulative incidence of methylation of these 2 genes was 85% (28/33). The APC and cyclin D2 gene promoters were both unmethylated in the aspiration fluids from 19 women with nonmalignant breast disease.Conclusions.-Breast aspiration fluid CEA concentration and the methylation of the APC gene promoter 1A and the promoter region of the cyclin D2 gene can be used as tumor markers to overcome some of the limitations of aspiration cytology. In combination with the mammogram and physical examination, assays for these markers could be used to help determine a definitive diagnosis when cytologic results are suspicious for malignancy.     

Diagnostic value and biological significance of antibody-coated bacteria in urine

The incidence of antibody-coated bacteria (ACB) in the urinary sediments as an indication of the site of urinary tract infections (UTI) was investigated in 103 adult subjects with persistent bacteriuria by means of a direct immunofluorescence technique.     

多种肿瘤标志物在胰腺癌中的诊断价值及相关性研究

目的：探讨血清肿瘤标志物联合检测对胰腺癌的诊断价值及相关性。 方法：选取2013年1月至2016年5月我院胰腺癌患者146例,非胰腺癌患者128例和健康体检者124例,放射免疫分析仪检测各组血清CA19-9、CA242、CA50、CA125、CEA及TSGF水平,并进行各组间比较。绘制受试工作特征曲线（ROC）分析各肿瘤标志物在胰腺癌患者中的诊断价值,线性相关分析各肿瘤标志物的相关性。应用多元Logistic回归模型分析胰腺癌的独立危险因素。结果：胰腺癌组血清CA19-9、CA242、CA50、CA125、CEA及TSGF水平明显高于对照组和非胰腺癌组,差异有统计学意义（P<0.05或P<0.01）。Ⅳ期和Ⅲ期患者血清CA19-9、CA242、CA50、CA125及TSGF水平明显高于Ⅰ期和Ⅱ期（P<0.01）,且Ⅳ期患者血清CA19-9、CA242、CA125及CEA水平明显高于Ⅲ期（P<0.01）。胰腺癌组血清CA19-9、CA242、CA50、CA125、CEA及TSGF的阳性率明显高于对照组和非胰腺癌组（P<0.01）。ROC曲线显示,血清CA19-9的AUC高于其他单项指标,其最佳临界值、灵敏度和特异度分别为114.5 U/ml、81.2%和79.3%。6项联合检测的诊断效能均优于各单项检测,其灵敏度和特异度分别为92.4%和76.5%。相关性分析显示,血清CA19-9与CA242、CA50及CA125均呈正相关（r=0.703,P=0.005;r=0.572,P=0.024;r=0.439,P=0.036）。多元Logistic回归分析显示,吸烟、不正确的饮食习惯、糖尿病史、胆系疾病史及CA19-9、CA242、CEA进入回归模型,其OR值及95%CI分别为1.717（0.736～2.359）、2.865（2.217～3.685）、2.614（2.186～3.127）、3.527（2.842～4.377）、4.214（3.570～4.962）、2.315（2.114～2.539）、1.876（1.175～2.852）。 结论：血清肿瘤标志物联合检测有助于提高早期胰腺癌诊断的准确性,吸烟、不正确的饮食习惯、糖尿病史、胆系疾病史及高水平的CA19-9、CA242、CEA是胰腺癌的独立危险因素。     

血清甲胎蛋白联合癌胚抗原检测在肝癌诊断中的应用价值（附125例报告）

目的探讨血清甲胎蛋白联合癌胚抗原检测在原发性肝癌和转移性肝癌诊断中的应用价值。方法回顾性分析我院2003年7月～2006年3月收治的125例肝癌患者的临床资料,同时测定他们和65例健康人血清中的血清甲胎蛋白和癌胚抗原含量。结果肝癌组血清甲胎蛋白和癌胚抗原含量及阳性率明显高于正常对照组,且转移性肝癌中癌胚抗原含量明显高于原发性肝癌。结论检测血清中血清甲胎蛋白和癌胚抗原的含量,对肝癌的诊断有很高的价值,对鉴别肝癌的类型具有一定的指导意义。     

Persistent histidine-rich protein 2, parasite lactate dehydrogenase, and panmalarial antigen reactivity after clearance of Plasmodium falciparum monoinfection

We tested 240 patients with Plasmodium falciparum monoinfection for persistent parasite antigenemia after successful standardized antimalarial therapy by using the ICT Malaria Pf/Pv and OptiMAL-IT assays that detect the malaria antigens Plasmodium falciparum histidine-rich protein 2 (HRP2) and parasite lactate dehydrogenase (pLDH), respectively, as well as a panmalarial antigen (PMA). The patients were screened for antigenemia on days 0, 3, 7, and 14 of follow-up. On day 0, all 240 patients showed positive reactivity with both assays. Of the 229 cases with negative parasitemia on day 3, persistent antigenemia was observed in 207 (90.4%) of the cases: 188 (82.1%) for HRP2 antigen and 75 (32.8%) for PMA. There was a gradual decrease in antigenemia on follow-up to day 14; however, the drop in reactivity to PMA was less than that for HRP2 antigen. In contrast to HRP2 antigenemia, there was a significant decrease in pLDH antigenemia to 38.4% and to 14.8% (PMA) on day 3 (P < 0.03). The pLDH antigenemia level dropped further to 14.8% on day 7. There was no significant association of persistent antigenemia with gametocytemia. One case with gametocytemia was negative for both the antigens. In conclusion, the OptiMAL-IT assay is more sensitive than the ICT Malaria Pf/Pv test for monitoring therapeutic responses after antimalarial therapy since the LDH activity ceases when the malarial parasite dies.     

High expression of CEACAM19, a new member of carcinoembryonic antigen gene family,in patients with breast cancer

Carcinoembryonic antigen (CEA) family members play important roles in malignancies and are introduced as biomarkers in different types of cancers. Among them CEACAM19 (CEAL1) gene, a new member of the CEA family, remains to be fully elucidated. The aim of this study was investigating the mRNA expression level of CEACAM19 in tumor samples of breast cancer patients compared to breast tissue of normal individuals. We evaluated the expression level of this gene in 75 breast tumors by using real-time quantitative PCR. Also, we studied the correlation between CEACAM19 expression and clinicopathological features and hormone receptors status, including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 of patients. Out of the enrolled patients, six of them (7.9%) showed low expression, ten (13.2%) showed normal expression and 59 (77.6%) showed high expression of CEACAM19. There was a significant correlation between high expression of CEACAM19 gene in tumor samples compared to normal tissues (P = 0.039). No significant correlation was seen between clinicopathological factors and disease-free survival with mRNA levels of CEACAM19 in tumor samples, while the difference between the expression of CEACAM19 in ER/PR-positive and ER/PR-negative breast cancer patients was statistically significant (P = 0.046). In conclusion, CEACAM19 showed high expression in tumor samples compared to normal mammary tissue. In addition, CEACAM19 may represent as a novel therapeutic target in certain subgroups of breast cancer patients such as ER/PR-negative. Critical roles of CEA proteins in tumor progression may nominate them as robust potential targets for therapeutic intervention in near future.