Cytokeratins as serum markers in egyptian bladder cancer. A comparison of CYFRA 21-1, TPA and TPS

Cytokeratins (CKs) have been shown to be overexpressed in bladder cancer and to be valuable as tumor markers. The present study was designed to evaluate the single and combined use of three cytokeratin fragments, CYFRA 21-1, TPA, and TPS, in serum of Egyptian bladder cancer patients. The study subjects comprised 40 healthy controls, 30 patients with benign bladder diseases, and 60 patients with histologically confirmed primary bladder cancer. The cutoff was set at 95% specificity versus benign bladder diseases, resulting in cutoff values of 2.93 ng/mL for CYFRA 21-1, 158 U/L for TPA and 143.7 ng/mL for TPS. With 41% true positive results CYFRA 21-1 had a higher sensitivity than TPA (32%) and TPS (27%). Evaluation by histological findings revealed a highest sensitivity of CYFRA 21-1 (46%) in transitional cell carcinoma (TCC) followed by TPA (27%) and TPS (21%). Also in adenocarcinoma CYFRA 21-1 showed the highest sensitivity (38%) followed by TPA (32%) and TPS (28%). A high percentage (41.6%) of Egyptian bladder cancers is represented by squamous cell carcinoma (SCC). In this population TPS showed the highest sensitivity (69%), followed by CYFRA 21-1 (54%) and TPA (41 %). The sensitivity of each of the three markers increased with advancing tumor stage and increasing tumor grade. Combined use of two of the three markers did not raise the sensitivities obtained by single determination of CYFRA 21-1. The present study suggests that serum CYFRA 21-1 could be a marker of choice in bladder cancer.     

NSE、CEA 和CYFRA21-1 测定对胸腔积液的诊断价值

目的:探讨神经元烯醇化酶(NSE)、癌胚抗原(CEA)和细胞角蛋白19(CYFRA21-1)测定对胸腔积液的诊断价值。方法:选择我院2009年4月～2011年9月收治的胸腔积液患者89例作为研究对象,按照胸腔积液性质分为两组,良性组47例,恶性组42例,对两组的NSE、CEA和CYFRA21-1测定结果进行比较分析。结果:恶性组患者血清和胸腔积液中NSE、CEA和CYFRA21-1水平均明显高于良性组,组间差异有统计学意义(P<0.05);NSE、CEA和CYFRA21-1联合检测对恶性胸腔积液的敏感性均明显高于单独NSE、CEA和CYFRA21-1检测,差异有统计学意义(P<0.05)。结论:NSE、CEA和CYFRA21-1测定对胸腔积液具有临床诊断价值,且三者联合检测能够明显提高诊断敏感性。     

血清及胸腔积液中CA19-9、SCC-Ag及CYFRA21-1对肺癌诊断意义的对比研究

目的:探讨肺癌患者血清及胸腔积液中的糖蛋白抗原19-9(CA19-9)、鳞状细胞癌抗原(SCC-Ag)和细胞角蛋白19片段(CYFRA21-1)对肺癌的诊断意义。方法:选取2016年1月到2017年6月在我院接受治疗的肺癌患者67例作为肺癌组,另选取我院同期收治的肺良性病变患者55例纳入良性病变组。采用电化学发光法检测并对比两组患者血清及胸腔积液中的CA19-9、SCC-Ag和CYFRA21-1水平,比较所有研究对象血清及胸腔积液中CA19-9、SCC-Ag和CYFRA21-1的阳性率并分析其诊断价值。结果:肺癌组患者血清及胸腔积液中的CA19-9、SCC-Ag和CYFRA21-1水平显著高于良性病变组,有统计学差异(P0.05)。CA19-9、SCC-Ag和CYFRA21-1在胸腔积液中的阳性率高于在血清中的阳性率,有统计学差异(P0.05)。胸腔积液中CA19-9、SCC-Ag和CYFRA21-1单项检测对肺癌的灵敏度显著高于血清检测,血清及胸腔积液中CA19-9、SCC-Ag和CYFRA21-1三项联合检测的灵敏度、特异性、阳性预测值均高于单项检测,差异均有统计学意义(P0.05)。结论:肺癌患者血清及胸腔积液中CA19-9、SCC-Ag和CYFRA21-1呈现高表达,三项指标联合检测可提高诊断肺癌的灵敏度、特异性和阳性预测值。     

多种血清肿瘤标志物联合检测对肺癌诊断的临床意义分析

目的:探讨CA125、CYFRA21-1、CEA、NSE、AFP联合检测对肺癌的诊、诊断的敏感度以及特异性。方法:对我院收治的确诊为肺癌的患者选取120例作为A组,同期选择肺部良性病变患者61例作为B组,以及50例健康体检患者作为C组,将三组研究对象分别进行CA125、CYFRA21-1、CEA、NSE、AFP的检测。结果:A组患者CA125、CYFRA21-1、CEA、NSE、AFP的血清中含量明显高于B组以及C组(P<0.05);五种标记物联合检测的敏感度明显高于单一标志物的敏感度(P<0.05),但其特异性有明显的降低(P<0.05)。结论:采用CA125、CYFRA21-1、CEA、NSE、AFP联合检测,对肺癌的早期诊断以及治疗预后有较好的指导作用。     

荧光原位杂交应用于尿路上皮癌尿液早期诊断的研究进展

尿路上皮癌（urothelial carcinoma,uc）是泌尿系统最常见恶性肿瘤之一,早期诊断是提高该类疾病疗效的关键所在,荧光原位杂交（fluorescencein situ hybridization,FISH）通过尿液来检测UC,具有快速、无创伤性、敏感度高和特异性强等优点。FISH提高了尿细胞学在低级别或浅表性膀胱UC诊断的敏感性,且减少了血尿、尿路感染及膀胱内灌注治疗等对细胞形态的影响而引起的假阳性,提高检测的特异性。对于诊断上尿路UC,FISH的敏感性与特异性更高。膀胱UC患者9号染色体p16抑癌基因丢失与复发明显相关。FISH既能预测膀胱UC的复发性,更能监测UC的复发,但仍需大样本、多中心的前瞻性研究。本文将FISH在膀胱UC、上尿路UC早期诊断以及膀胱UC术后监测等方面的临床应用研究报道进行综述。     

BTA-TRAK combined with urinary cytology is a reliable urinary indicator of recurrent transitional cell carcinoma (TCC) of the bladder

This study evaluated the diagnostic accuracy of BTA-TRAK in combination with urinary cytology (UC) in the follow-up of patients with a history of transitional cell carcinoma (TCC) of the bladder. The overall sensitivity of BTA-TRAK, UC and the two tests combined for the detection of recurrences was 82.7% (48/58), 84.2% (48/57) and 91.2% (52/57), respectively. BTA and UC showed comparable sensitivity for superficial recurrences (76.7% (33/43) and 78.5% (33/42), respectively) and for invasive recurrences (100% (15/15)); when the two tests were used in combination, the sensitivity for superficial lesions increased to 88% (37/42). BTA-TRAK was more sensitive than UC for G1 recurrences (81.2% (13/16) vs. 68.7% (11/16)), and when the two tests were combined the sensitivity increased to 87.5% (14/16). The sensitivity of the combination was 100% (15/15) for G3 lesions. The differences in urinary BTA-TRAK levels between patients with recurrences and those without evidence of disease were statistically significant (Wilcoxon's test, p<0.05); among patients with recurrences BTA levels were significantly higher in the invasive and poorly differentiated subtypes. In the series of patients studied by us, BTA-TRAK combined with UC was shown to be a non-invasive, accurate test to predict TCC recurrences. Periodic measurement of BTA-TRAK combined with urinary cytology seems to provide additional information for the monitoring of patients treated for TCC; however, due to the presence of false positive and false negative results, this test cannot replace cystoscopy. In a selected group of patients it could, if combined with cytology and ultrasonography and if correctly used and interpreted, orient the timing and indication for cystoscopy.     

Ras oncogene mutations in urine sediments of patients with bladder cancer

Early detection of bladder cancer is particularly important since it dramatically affects the survival rates. However, neither urinary cytology nor tumor markers that are currently used are sensitive enough for the early detection of bladder cancer or recurrent disease. The ras genes are frequently mutated in cancer. In this study, we investigated the diagnostic potential of ras mutation analysis in urinary sediments of patients with bladder cancer using a single-strand conformation polymorphism analysis and polymerase chain reaction. Mutation in codon 12 of the H-ras gene was observed in 39% of the patients. Our results indicate that this approach may significantly improve diagnostic sensitivity in detecting bladder tumors.     

Serum CYFRA21-1 as a prognostic marker for patients with undifferentiated nasopharyngeal carcinoma

The purpose of this study was to evaluate the potential of serum CYFRA21-1 and carcinoembryonic antigen (CEA) as prognostic markers in patients with undifferentiated nasopharyngeal carcinoma. Sixty-one patients who received definitive radiotherapy/chemoradiotherapy were analysed retrospectively. We investigated the association of the follow-up results with pretreatment level, post-treatment level and change of serum CYFRA21-1 and CEA, respectively. Patients with low pretreatment CYFRA21-1 had a significantly better overall survival. There were no significant associations among the remaining serum markers, and the survival and recurrence rates on multivariate analysis. The present study shows that pretreatment CYFRA21-1 level is a potential factor for predicting long-term survival.     

Prognostic value of cytokeratin 19 fragment (CYFRA 21-1) and cytokeratin-positive cells in bone marrow samples of breast cancer patients

The aim of this study was to investigate the relationship between the detection of micrometastatic cells by immunocytochemistry (ICC) with an anticytokeratin antibody and cytokeratin fragment (CYFRA 21-1) expression detected by an immunofluorescent assay in bone marrow of breast cancer patients. Micrometastatic CK+ cells were screened with a pancytokeratin antibody A45 B/B3 from bone marrow aspiration samples of 102 breast cancer patients (65 primary tumors, 10 local recurrences and 27 distant metastases). CYFRA 21-1 levels were assessed in bone marrow supernatant of these patients before collection of the mononucleated interface cells on a Ficoll-Hypaque density gradient and in 20 control patients. CYFRA 21-1 and CK+ cell detection by ICC were both correlated with clinical stage. CYFRA 21-1 was significantly elevated in patients with micrometastatic disease detected by ICC: 4.77 ng/mL (+/- 10.87 SD) versus 1.00 ng/mL (+/-1.36 SD) in patients with negative ICC (p=0.01). In univariate analysis, a CYFRA 21-1 value > or =1 ng/mL and the presence of CK+ cells were associated with a poorer survival for patients with stage I to III breast cancer (n=65). On multivariate analysis, only pathological nodal status and presence of CK+ cells in bone marrow were independent prognostic factors for overall survival. In conclusion, in this series CYFRA 21-1 was correlated with detection of CK+ cells by ICC in bone marrow, but cannot replace ICC. The presence of CK+ cells in bone marrow remains a strong independent prognostic factor in primary breast cancer.     

荧光原位杂交应用于尿路上皮癌尿液早期诊断的研究进展

尿路上皮癌(urothelial carcinoma,UC)是泌尿系统最常见恶性肿瘤之一,早期诊断是提高该类疾病疗效的关键所在,荧光原位杂交(fluorescence in situ hybridization,FISH)通过尿液来检测UC,具有快速、无创伤性、敏感度高和特异性强等优点。FISH提高了尿细胞学在低级别或浅表性膀胱UC诊断的敏感性,且减少了血尿、尿路感染及膀胱内灌注治疗等对细胞形态的影响而引起的假阳性,提高检测的特异性。对于诊断上尿路UC,FISH的敏感性与特异性更高。膀胱UC患者9号染色体p16抑癌基因丢失与复发明显相关,FISH既能预测膀胱UC的复发性,更能监测UC的复发,但仍需大样本、多中心的前瞻性研究。本文将FISH在膀胱UC、上尿路UC早期诊断以及膀胱UC术后监测等方面的临床应用研究报道进行综述。     

血清CEA、NSE、CYFRA21-1 联合支气管活检在周围型肺癌诊断鉴别中的应用

目的:探讨血清肿瘤标志物癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段(CYFRA21-1)联合经纤维支气管镜肺活检(TBLB)在周围型肺癌诊断鉴别中的应用价值。方法:选择2012年9月到2014年9月在我院临床确诊的402例周围型肺癌患者。检测所有患者的血清CEA、NSE和CYFRA21-1的浓度及分析TBLB检测结果,分析不同病理类型和不同病灶直径大小时各项检测指标及联合检测的阳性检出率。结果:所有肺癌患者中,血清CEA、NSE、CYFRA21-1和TBLB的阳性检出率分别为51.74%,35.07%,41.79%和60.70%。四项指标联合检测的阳性检出率为89.05%,明显分别高于四项指标的阳性检出率(均P0.05)。腺癌、鳞癌、小细胞肺癌及其他类型肺癌组四项联合检测的阳性检出率明显高于四项单独检测(均P0.05)。病灶直径为2 cm、2-6 cm和6 cm时,四项联合检测的阳性检出率明显高于四项单独检测(均P0.05)。结论:血清CEA、NSE、CYFRA21-1联合TBLB检测周围型肺癌较单项检测,阳性检出率高,值得在临床上推广应用。     

Serum level of cytokeratin 19 fragment (CYFRA 21-1) indicates tumour stage and prognosis of squamous cell carcinoma of the oesophagus

To determine the clinical efficacy of serum concentration of cytokeratin 19 fragment (CYFRA 21-1), sera from 66 patients with oesophageal squamous cell carcinoma were examined, and 54 surgically resected specimens were immunohistochemically stained for cytokeratin 19 (CK-19). The patients with positive CK-19 staining in the tissues of their carcinomas had significantly higher serum CYFRA 21-1 levels compared with those with negative CK-19 staining. When the cut-off value was defined as 2.0 ng/mL, CYFRA 21-1 had a higher positive ratio than that of either squamous cell carcinoma antigen (SCC-Ag) or carcinoembryonic antigen (CEA). Serum CYFRA 21-1 level increased significantly along with the clinical stages. In addition, serum CYFRA 21-1 level served as a prognostic factor for patients with oesophageal carcinoma after surgery, whilst SSC-Ag and CEA is not connected with the outcome. These findings suggest that the serum CYFRA 21-1 probably originated from the tumour tissue is an important marker for determining the stage and outcome of oesophageal carcinoma.     

肺癌患者血清CEA、CYFRA21-1和NSE的检测及临床意义

目的探讨外周血癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)和神经元特异性烯醇化酶(NSE)的检测对肺癌的诊断、病理分型和疗效判断的临床用价值。方法采用化学发光法检测了62例肺癌患者、54例良性肺部疾病患者、36例健康人、40例肺癌患者手术前后血清CEA、CYFRA21-1和NSE的水平。结果肺癌患者手术前血清CEA、CYFRA21-1和NSE的含量明显高于良性肺部疾病组及正常对照组(P0.01)。鳞癌组、腺癌组和小细胞癌组之间肿瘤标志物CEA、CYFRA21-1和NSE水平差异有统计学意义。CEA阳性率以腺癌组最高(84%),CYFRA21-1阳性率以鳞癌组最高(85.2%),NSE阳性率以小细胞癌组最高(80.0%)。手术治疗后未复发转移组CEA、CYFRA21-1和NSE水平低于术前,而复发转移组与术前比变化不显著(P0.05)。结论血清CEA、CYFRA21-1和NSE的检测对不同病理类型肺癌患者的诊断、病情检测及疗效判断有较好的临床参考价值。     

血清CEA、CA19-9、CYFRA21-1与结直肠腺癌的相关性分析

目的:探究血清癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原19-9、细胞角蛋白19片段(cytokeratin19 fragements,CYFRA21-1)与结直肠腺癌的病理相关性。方法:选择于我院接受治疗的80例结直肠腺癌患者为病例组,选择同期于我院接受治疗的50例良性结直肠病变患者为良性对照组,选择我院体格检查的50例健康个体为对照组,分别采集三组个体的血样并进行CEA、CA19-9以及CYFRA21-1水平的检测,并比对三组个体上述因子阳性表达率、因子水平,同时分析三种因子同结直肠腺癌患者TNM分期相关性,最后探究三种因子对结直肠腺癌的诊断价值。结果:(1)以CEA≥2.805μg/L、CA19-9≥39 U/m L、CYFR21-1≥3.3 ng/mL为临界值,结果显示病例组CEA阳性率51.25%,CA19-9阳性率31.25%,CYFR21-1阳性率40.00%,明显高于良性组的10.00%、20.00%和10.00%,高于对照组的8.00%、12.00%和2.00%(P<0.05);(2)比较显示病例组患者的CEA、CA19-9以及CYFR21-1水平明显高于良性对照组以及对照组(P<0.05),良性对照组CEA、CA19-9以及CYFR21-1水平明显高于对照组(P<0.05);(3)比较显示IV期结直肠腺癌患者CEA、CA19-9以及CYFRA21-1水平明显高于III期以及I+II期(P<0.05),III期三种因子水平明显高于I+II期(P<0.05);(4)CEA对结直肠腺癌诊断一致性71.25%,灵敏度65.00%,特异度90.00%;CA19-9诊断一致性46.25%,灵敏度35.00%,特异度80.00%;CYFRA21-1诊断一致性55.00%,灵敏度46.67%,特异度80.00%;联合诊断一致性95.00%,灵敏度95.00%,特异度95.00%。结论:血清CEA、CA19-9以及CYFRA21-1对结直肠腺癌具有较明确的诊断价值,不同病理分期患者中表达差异明显,可以考虑将联合诊断作为结直肠腺癌鉴别方式之一,推广于临床中。     

Detection of BRAF Mutation in Urine DNA as a Molecular Diagnostic for Canine Urothelial and Prostatic Carcinoma

Urothelial carcinoma (UC) of the lower urinary tract and prostatic carcinoma (PC) are aggressive genitourinary cancers in dogs, characterized by invasion to surrounding tissues and high metastatic potential. Current diagnosis of canine UC and PC requires histopathological examination of a biopsy. Such specimens require specialized medical equipment and are invasive procedures, limiting the availability of diagnosis by histopathology for many canine patients. Access to a non-invasive means to confirm diagnosis is currently an unmet need. Recently, the canine BRAF V595E mutation was detected in ~80% of canine UCs and PCs. In this study, we developed a droplet digital PCR (ddPCR) assay for detection of the canine BRAF V595E mutation in canine urogenital tumors. The assay was evaluated in DNA samples prepared from biopsy specimens of UC (n = 48) and PC (n = 27), as well and non-neoplastic bladder epithelium (n = 38). In addition the assay was assessed for use with DNA isolated from free catch urine samples derived from canine patients with UC (n = 23), PC (n = 3), as well as from dogs with cystitis and healthy controls (n = 37). In all cases the sensitivity to detect the mutant allele was compared with conventional Sanger sequencing. ddPCR had superior sensitivity for detection of the V595E mutation: 75% of UC, 85% of PC, and 0% of control samples were mutation positive, respectively, and the V595E mutation was detected at a level as low as just 1 in 10,000 alleles (~0.01%). Furthermore, the ddPCR assay identified the mutation in free catch urine samples from 83% of canine UC and PC patients, demonstrating its utility as a non-invasive means of diagnosis. We have shown that ddPCR is a sensitive molecular technique with the potential to facilitate accurate and non-invasive means of canine UC and PC diagnosis.     

CYFRA 21-1 in non-small cell lung cancer--standardisation and application during diagnosis

There is no ideal tumour marker at present. The clinical application of CYFRA 21-1 is possible once a thorough standardisation process is carried out. Standardisation is achieved by determining the reference range in asymptomatic population, benign and malignant lung diseases, and benign and malignant diseases of other organs. Furthermore, it depends on knowledge of research population characteristics, patient medical histories and individual diagnostic procedure results, the size of research target samples and the clinically defined control groups. The cut-off level of CYFRA 21-1 for non-small cell lung cancer (NSCLC) is 1.72 ng/mL in the Croatian population. It is based on the clinically applicable sensitivity of 78% and specificity of 95% in benign lung diseases. The cut-off value is verified by clinical findings. For clinicians the level of CYFRA 21-1 is an early sign of NSCLC in relation to all the benign lung diseases and all the benign diseases of other organs, of which it was confirmed that they can influence the above level, provided that NSCLC is verified using standard diagnostic methods. The level of CYFRA 21-1 is also influenced by the time of sampling in relation to other diagnostic invasive procedures. The marker is clinically applicable if clinical findings verify it; otherwise, it is useless. This research has involved 343 healthy persons, 474 patients with a benign disease and 4440 patients with a malignant disease, 2453 of whom suffer from NSCLC. The sensitivity of CYFRA 21-1 in NSCLC is 78%, in squamous cell lung cancer (SQC) 84.6%, in adenocarcinomas (AD) 74.3% and in large cell lung cancer (LCC) 75.3%. The level of CYFRA 21-1 differs significantly between healthy persons, benign and malignant diseases (p<10(-3)). There are differences between the three histological types of NSCLC (p<10(-6)) and according to T and N (p<10(-3)). The level of CYFRA 21-1 prompts clinicians to repeat the clinical procedure during diagnosis, and helps to detect the disease earlier and implement treatment in NSCLC. We have achieved high concordance between marker findings and clinical diagnostic.     

非小细胞肺癌患者血清CYFRA21-1、VEGF及CEA的表达及与临床病理特征的相关性研究

目的:研究非小细胞肺癌(NSCLC)患者血清细胞角蛋白19片段(CYFRA21-1)、血管内皮生长因子(VEGF)、癌胚抗原(CEA)的表达及与临床病理特征的相关性。方法:选取2015年12月至2016年4月在我院接受治疗的NSCLC患者120例作为观察组,另选取同期在我院接受治疗的肺部良性病变患者50例作为良性对照组,比较两组患者血清中CYFRA21-1、VEGF及CEA的表达,分析观察组患者血清中CYFRA21-1、VEGF及CEA的表达与临床病理特征之间的关系,采用Pearson相关系数分析观察组患者血清中CYFRA21-1、VEGF、CEA的相关性。结果:观察组患者血清中的CYFRA21-1、VEGF及CEA水平均高于良性对照组(P0.05)。鳞状细胞癌患者血清中CYFRA21-1水平高于腺癌患者,CEA水平低于腺癌患者(P0.05),鳞状细胞癌患者和腺癌患者血清中VEGF水平比较无统计学差异(P0.05)。TNM分期为III-IV期的观察组患者血清中CYFRA21-1、VEGF及CEA水平均明显高于I-II期患者,有统计学差异(P0.05)。经Pearson相关系数分析显示,观察组患者血清中CYFRA21-1与VEGF、CEA呈正相关(r=0.512,0.423,P=0.000,0.000),VEGF与CEA呈正相关(r=0.452,P=0.000)。结论:NSCLC患者血清中CYFRA21-1、VEGF及CEA呈高表达,且CYFRA21-1、CEA与病理类型和TNM分期有关,VEGF与TNM分期有关,且三种指标存在一定的相关性。     

CEA和CYFRA21-1在原发性肺癌诊断中的应用价值分析

目的:评价血清癌胚抗原(carcinoembryonic antigen,CEA)和细胞角蛋白19的片段(CYFRA21-1)水平对原发性肺癌的诊断价值。方法:回顾性分析2012年5月~2013年5月我科收治的329例肺癌患者和192例肺部良性病变患者的临床资料。结果:肺癌患者血清CEA或CYFRA21-1水平随着肺癌的分期呈现逐渐上升的趋势(P0.001,P0.01)。以血清CEA≥3.4μg/L作为诊断条件诊断肺癌的灵敏度、特异度和阳性预计值预计值分别为67%、62%和75.2%;以血清CYFRA-21≥5.0 ug/L作为诊断条件诊断原发性肺癌的灵敏度、特异度和阳性预计值预计值分别为48%、87%和86.3%;以血清CEA≥3.4 ug/L和CYFRA-21≥5.0 ug/L共同作为诊断条件推断原发性肺癌的灵敏度、特异度和阳性预计值预计值分别为48%、87%和86.3%;良性肺部疾病患者中血清CEA和CYFRA-21水平同时升高者只有2%。结论:血清CEA≥3.4 ug/L和CYFRA-21≥5.0 ug/L同时升高对肺癌有具有重要的诊断价值,可有效的鉴别原发性肺癌与其它良性病变。