血清细胞角蛋白19片段和恶性肿瘤特异性生长因子联合检测对鼻咽癌的诊断价值

目的探讨血清细胞角蛋白19片段(CYFRA21-1)和恶性肿瘤特异性生长因子(TSGF)联合检测对鼻咽癌(NPC)的临床诊断价值.方法采用电化学发光免疫分析等技术,检测正常对照组50例、良性疾病组25例、NPC组82例血清中的CYFRA21-1及TSGF表达水平.结果NPC组CYFRA21-1、TSGF敏感性分别为48.8%、57.3%,其测定值均明显高于正常对照组和良性疾病组(均P<0.01).CYFRA21-1、TSGF两项联合检测可使敏感性提高到74.3%,且特异性没有明显下降.结论CYFRA21-1、TSGF可作为NPC临床诊断的血清肿瘤标志物,两项联合检测结果更理想.     

A study of a new tumour marker,CYFRA 21-1, in squamous cell carcinoma of the head and neck,and comparison with squamous cell carcinoma antigen

CYFRA 21-1 (CYFRA) is a newly developed tumour marker which is useful in evaluating large cell lung carcinoma, especially the squamous cell type. The purpose of this study was to assess the clinical value of CYFRA for squamous cell carcinoma of the head and neck and compare the results with squamous cell carcinoma antigen (SCCA). Serum levels of CYFRA were measured in 168 patients with a newly diagnosed head and neck squamous carcinoma. In addition, 77 patients without evidence of neoplasm were included as controls. At the same time, SCCA was also determined. The cut-off values of CYFRA and SCCA, determined at the 95th percentile of the standard Gaussian variate of controls, were 2.48 ng/ml and 1.49 ng/ml respectively. The diagnostic sensitivity of CYFRA was superior to that of SCCA, especially for nasopharyngeal carcinoma. The sensitivity of CYFRA for nasopharyngeal carcinoma was much higher (58.3%) than that of SCCA (15.5%). However, the sensitivity of CYFRA is not satisfactory in all types of squamous carcinoma. For oral cancer, the sensitivity is only 25.6%. CYFRA is a useful serum marker for patients with certain types of head and neck squamous carcinoma, such as nasopharyngeal carcinoma and hypopharyngeal carcinoma. In addition, CYFRA may be also useful in monitoring recurrence of certain types of SCCHN, which are sometimes difficult to detect.     

喉癌患者血清细胞角蛋白片段21-1检测及临床意义

目的 :探讨细胞角蛋白片段 2 1 1(CYFRA2 1 1)在喉癌患者血清中的表达及其临床意义。方法 :采用酶联免疫吸附法对 2 5例喉癌患者手术前后的血清CYFRA2 1 1进行检测 ,并与 2 0例喉良性病变患者进行对比。结果 :喉癌患者血清CYFRA2 1 1阳性率为 6 0 .0 % ,术前CYFRA2 1 1水平为 (5 .14± 1.82 ) μg/L ,显著高于喉良性病变 (2 .17± 0 .6 8) μg/L(P <0 .0 5 )。术后血清CYFRA2 1 1水平显著下降并低于正常水平。术后复发者血清CYFRA2 1 1水平再次上升。CYFRA2 1 1含量与喉癌患者的年龄、性别及肿瘤部位无关 ;高水平血清CYFRA2 1 1与喉癌临床分期、病理分级及淋巴结转移相关 ,分化愈差 ,CYFRA2 1 1含量越高。结论 :血清CYFRA2 1 1可望作为喉癌诊断、预后判定和术后随访有用的生物学指标。     

Analytical and clinical evaluation of CYFRA 21-1 by electrochemiluminescent immunoassay in head and neck squamous cell carcinoma

This paper attempts to evaluate the clinical usefulness of CYFRA 21-1 as a serum tumour marker in patients with head and neck squamous cell carcinoma (HNSCC). The serum concentration of CYFRA 21-1 was measured utilizing a new electrochemiluminescent immunoassay (ECLIA) in 142 patients with HNSCC before and after treatment, 68 patients with benign tumours of the head and neck, and 50 healthy controls. Serum levels of CYFRA 21-1 in patients with HNSCC were significantly higher than those of benign tumours and healthy controls (p < 0.001). The diagnostic sensitivity and specificity of CYFRA 21-1 for HNSCC were 62 per cent and 100 per cent, respectively. The positive rates of CYFRA 21-1 increased with progression of HNSCC, serum CYFRA 21-1 levels were related to the tumour stage expressed by primary tumour (T) and nodal status (N) (p < 0.001), but not related to patient age, gender, smoking and drinking habit, or histopathological grade (p > 0.05). Post-treatment levels of CYFRA 21-1 in HNSCC decreased significantly (p < 0.001). Among 38 patients with clinical or radiological evidence of a recurrence during follow-up, 78.9 per cent (30 of 38) showed an increase in CYFRA 21-1. The analytical ECLIA performance for serum CYFRA 21-1 provides a new means of clinical assessment for HNSCC. The results of ECLIA suggest that the serum marker CYFRA 21-1 is valuable not only for diagnosis but also for close monitoring of patients with HNSCC.     

头颈鳞状细胞癌患者血清Cyfra21-1检测的临床意义

目的 探讨血清Cyfra21-1在头颈鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的临床意义.方法 采用双抗体夹心ELISA法对随机选取的60例HNSCC患者,40例甲状腺良性肿瘤患者,20名健康对照组进行血清Cyfra2l-1检测.应用SPSS 11.5统计软...     

Study of cyfra 21-1, a tumor marker, in head and neck squamous cell carcinoma

OBJECTIVES: We performed a prospective study to determine the cutoff value and the prognostic value of Cyfra 21-1, a serum tumor marker, in head and neck squamous cell carcinoma (HNSCC). METHODS: The serum concentration of Cyfra 21-1 was measured in a group of 300 patients (group 1) with HNSCC, in a control group of 71 healthy subjects (group 2), and in a group of 73 patients with a nonmalignant tumor or inflammatory disease (group 3). The concentrations were compared between the various groups and subgroups; the cutoff value was calculated with a receiver operating characteristic curve. Furthermore, the serum concentrations of Cyfra 21-1 before treatment in the group of 300 patients were compared with the stage of the disease and with the evolution of the overall survival rate and the disease-free survival rate. Finally, to determine whether Cyfra 21-1 is an independent prognostic factor, we compared the concentrations, by a Cox model, with the classic prognostic factors of HNSCC. RESULTS: At the cutoff value of 1 ng/mL, the specificity was 94% and the sensitivity was 72%. The serum concentrations of Cyfra 21-1 were statistically correlated with the stage of the disease. The overall survival rate and the disease-free survival rate were lower in patients with high serum concentrations, and these differences were statistically significant (p < .001). The Cox model allows us to conclude that Cyfra 21-1 is a prognostic marker that is independent of other classic prognostic factors. CONCLUSIONS: Cyfra 21-1 is an interesting tumor marker that could be proposed for the early detection of HNSCC with a cutoff value of 1 ng/mL. Furthermore, Cyfra 21-1 can be considered an independent prognostic marker.     

Squamous cell carcinoma antigen in patients with cancer of the larynx

The purpose of this study was to evaluate the clinical usefulness of squamous cell carcinoma antigen (SCC Ag) in patients with squamous cell carcinoma of the larynx. Plasma specimens were obtained from 70 patients with cancer of the larynx before and after treatment and during follow-up. Disease status and the marker levels were determined blind to each other. Microparticle enzyme immunoassay (IMx SCC) was used to measure the SCC Ag level. Applying standard normal limits the sensitivity of the marker at diagnosis was 25.7%. SCC Ag levels were generally lower after therapy than before. Relapse occurred more often in patients with an abnormal pretreatment SCC Ag level, which was more frequent in those with nodal invasion. The marker level increased in 70% of the patients with relapse before the clinical detection of recurrence. SCC Ag is of limited usefulness in the primary diagnosis of cancer of the larynx, but is useful in detecting recurrence of cancer.     

Squamous cell carcinoma antigen in patients with cancer of the larynx.

The purpose of this study was to evaluate the clinical usefulness of squamous cell carcinoma antigen (SCC Ag) in patients with squamous cell carcinoma of the larynx. Plasma specimens were obtained from 70 patients with cancer of the larynx before and after treatment and during follow-up. Disease status and the marker levels were determined blind to each other. Microparticle enzyme immunoassay (IMx SCC) was used to measure the SCC Ag level. Applying standard normal limits the sensitivity of the marker at diagnosis was 25.7%. SCC Ag levels were generally lower after therapy than before. Relapse occurred more often in patients with an abnormal pretreatment SCC Ag level, which was more frequent in those with nodal invasion. The marker level increased in 70% of the patients with relapse before the clinical detection of recurrence. SCC Ag is of limited usefulness in the primary diagnosis of cancer of the larynx, but is useful in detecting recurrence of cancer.     

Antibody response against the epstein-barr virus-coded nuclear antigen2 (EBNA2) in nasopharyngeal carcinoma

Specific antibody responses against the Epstein-Barr virus-coded nuclear antigen2 (EBNA2) were evaluated. Thirty-five sera from pretreatment patients of nasopharyngeal carcinoma (NPC) and 12 from healthy adults were tested. Although the anti-EBNA2 response did not show any correlation with T stage, overall stage, or histopathology, it showed a correlation with the N stage of the disease. In a se-rological follow-up study, 17 (85%) of 20 patients showed a correlation on the change of antibody levels to EBNA2 and clinical progression. This suggests that EBNA2 serology might represent a useful marker relative to tumor status.     

鼻咽癌患者血清血管生长素水平的临床意义初探

目的:分析血管形成素(ANG)在鼻咽癌(NPC)患者血循环中的含量及其临床意义。方法:采用酶联免疫吸附试验(ELISA)测定42例NPC患者(NPC组)和30例健康者(对照组)血清ANG水平。结果:NPC组治疗前血清ANG水平为(371.4±123.5)μg/L,显著高于对照组的(292.5±74.2)μg/L(P<0.01),且血清ANG水平随着NPC临床分期的增加而升高(P<0.05);治疗后血清ANG水平为(340.6±112.4)μg/L,比治疗前明显降低(P<0.05),但仍高于对照组(P<0.05)。结论:NPC患者血清ANG水平升高,且其升高的程度与肿瘤的进展有关。     

Diagnostic sensitivity of 18fluorodeoxyglucose positron emission tomography for detecting synchronous multiple primary cancers in head and neck cancer patients

We assessed the sensitivity of positron emission tomography (PET) for detecting synchronous multiple primary cancers, particularly synchronous esophageal cancers in head and neck cancer patients. We retrospectively reviewed 230 head and neck cancer patients. All the patients routinely underwent the following examinations: urinalysis, occult blood, tumor marker detection [squamous cell carcinoma (SCC), cytokeratin fragment (CYFRA), and carcinoembryonic antigen (CEA)], esophagogastroduodenoscopy, colonoscopy (when CEA was high or occult blood was positive), abdominal ultrasonography, plain chest computed tomography (CT), and PET. Bronchoscopy was performed when CT revealed lung shadow of central region. Synchronous multiple primary cancers were detected in 42 (18.2%) patients. The diagnostic sensitivity of PET for synchronous primary cancers was as follows: esophagus, 7.6% (1/13); stomach, 25.0% (2/8); lung, 66.7% (4/6); head and neck, 75.0% (3/4); colon, 0% (0/1); kidney, 0% (0/1); and subcutaneous, 100% (1/1). The sensitivity of PET for detecting synchronous esophageal cancers is low because these are early-stage cancers (almost stage 0–I). Therefore, it is necessary to perform esophagogastroduodenoscopy for detecting synchronous esophageal cancers. PET is an important additional tool for detecting synchronous multiple primary cancers because the diagnostic sensitivity of PET in synchronous head and neck cancer and lung cancer is high. But PET has the limitation of sensitivity for synchronous multiple primary cancers because the diagnostic sensitivity of PET in synchronous esophageal cancer is very low.     

Circulating fragments of cytokeratin 19 in patients with head and neck squamous cell carcinoma

In head and neck squamous cell carcinoma a reliable serum marker of carcinogenesis should be of predictive value for the development of recurrent disease or a second primary tumour. At the moment, such a tumour marker is not available. Recently, elevated levels of cytokeratin 19-fragments (Cyfra 21-1) have been detected in the serum of patients with lung cancer, in particular with squamous cell carcinoma. Cytokeratin 19 is an intermediate cell filament protein expressed in simple epithelia and their malignant counterparts. Therefore, in this prospective study, a standardized sandwich enzyme-linked immunosorbent assay for soluble cytokeratin 19 fragments was tested in the serum of 20 patients with a previously untreated head and neck squamous cell carcinoma. The results were compared with that of 20 control individuals. Our results showed significantly higher Cyfra 21-1 concentrations in the serum of patients with cancer (10.21 ± 3.03 ng/ml) than the controls (7.2 ± 2.63 ng/ml). After radical treatment the marker levels dropped significantly to 1.65+ 1.07 ng/ml. Cyfra 21-1 appears to be of value as a circulating tumour marker for head and neck squamous cell carcinoma especially in monitoring disease control.     

Tumor markers in patients with head-neck carcinomas

The clinical relevance of the tumor-associated antigens SCC (squamous-cell carcinoma), CEA (carcinoembryonic antigen), and CA (carbohydrate antigen) 19-9 as tumor markers is evaluated. Twenty-six patients with squamous-cell carcinoma of the head and neck region were studied in a six-month period. Concentrations above 2 ng/ml (SCC), 5 ng/ml (CEA), and 37 U/ml (CA 19-9) are regarded as markers of abnormal activity. Elevated tumor markers were found only in 12-15%. No correlation between the serum levels and tumor localization, staging, grading, or general condition was detected for any of the markers. In the follow-up, they revealed no disease-related information despite treatment variation. The results obtained suggest that, given the present state of biochemical possibilities and considering the rather low sensitivity for head and neck cancer, the routine assessment of SCC, CEA, and CA 19-9 serum levels is of no account.     

Relevance of the new tumor marker SCC (squamous cell carcinoma antigen) for the diagnosis and follow-up control of squamous epithelial carcinoma of the head and neck

The SCC antigen, a tumour marker for squamous cell carcinoma, is already used for the diagnosis and follow-up of carcinoma of the cervix and the lungs. We determined the SCC antigen levels at the time of diagnosis and during therapy in 108 subjects with a squamous cell carcinoma of the head and neck. According to our results and those of other authors, the normal serum range of SCC lies between 0 and 2 ng/ml. Before therapy we found an increased titre in 38.9% of the subjects, being 6.2%, 30.8%, 47.2% and 76.2% for stages T1 to T4 respectively. Thus even some stage T3 and T4 tumours did not express the antigen. No correlation was found between the titre at the time of diagnosis and the grade of differentiation, the site of the tumour, the presence of lymph node or remote metastases, and the sex of the patient. After operation the titres returned to normal within 1 week, but after radiation or chemotherapy the titre decreased more slowly. In recurrent tumours we found a rising titre, which could be measured in several cases some weeks before the recurrence was visible. In the light of the costs and the yield of the method, we suggest determining the serum SCC antigen level once before therapy. If it is increased, subsequent estimates should be done during the succeeding years to allow early diagnosis of a recurrence of the tumour.     

POT1蛋白在人鼻咽癌细胞系及鼻咽癌组织中的表达及临床意义

目的探讨端粒保护蛋白1(protection of telomeres 1,POT1)在人鼻咽癌细胞系及鼻咽癌组织中的表达、细胞定位及临床意义。方法应用Western blot法检测POT1蛋白在人鼻咽癌系、人鼻咽上皮细胞系、鼻咽癌组织、癌旁组织中的表达;应用细胞免疫荧光检测POT1蛋白在鼻咽癌细胞中的定位。结果 POT1蛋白在人鼻咽癌细胞系CNE-1、5-8 F、CNE-2、6-10 B中的表达强度高于在人鼻咽上皮细胞系NP69中的表达强度,分别为2.8、2.3、1.9、1.5倍;POT1蛋白主要定位于细胞质;鼻咽癌组织中POT1蛋白表达量(0.6414±0.0979)明显高于癌旁组织中的表达量(0.4386±0.0912),两组比较有统计学意义(P<0.05);鼻咽癌组织中POT1蛋白表达强度与鼻咽癌的临床分期、T分期有关(P<0.05),但与患者年龄、性别、颈部淋巴结转移无关(P>0.05)。结论 POT1蛋白表达可能与鼻咽癌的发生与发展有关。     

Monitoring tumor recurrence with nasopharyngeal swab and latent membrane protein-1 and epstein-barr nuclear antigen-1 gene detection in treated patients with nasopharyngeal carcinoma

OBJECTIVES: Epstein-Barr virus (EBV) is closely related to nasopharyngeal carcinoma (NPC). Detection of EBV genomic DNA in a nasopharyngeal swab specimen may indicate the presence of NPC, and the EBV genomic DNA is only detected in patients with NPC and not in other head and neck cancers. This study aims to prove that detection of EBV genomic DNA by means of the latent membrane protein (LMP)-1 gene and the Epstein-Barr nuclear antigen (EBNA)-1 gene in the nasopharynx in NPC patients after radiation therapy indicates local recurrence of NPC. STUDY DESIGN: Prospective. METHODS: Nasopharyngeal swab with polymerase chain reaction (PCR)-based LMP-1 and EBNA-1 gene detection was used to monitor local recurrence in 84 NPC patients who completed radiation therapy. RESULTS: Of the 12 patients demonstrating positive LMP-1 and EBNA-1 gene, 11 had local recurrence, and 10 of them had early rT1 mucosal recurrence. Subsequent salvage nasopharyngectomy controlled local disease in nine. Only one local recurrence in the skull base failed to show LMP-1 gene initially. Detection of LMP-1 gene and later verification with EBNA-1 gene from nasopharyngeal swabs in NPC patients after radiation therapy predicted local recurrence with a sensitivity of 91.7% and a specificity of 98.6%. CONCLUSIONS: Nasopharyngeal swab with LMP-1 and EBNA-1 gene detection is a useful and reliable method to monitor local recurrence in NPC patients. It helps to detect recurrence early and may improve local control and enhance survival.     

鼻咽癌病人放射治疗前后天然杀伤细胞活性、白细胞介素-2水平改变的研究

目的：探讨鼻咽癌(nasopharyngeal carcinoma,NPC)病人放射治疗前后天然杀伤细胞(NK细胞)活性、白细胞介素—2(IL-2)水平的变化和肿瘤复发转移的关系。方法：选择139例首诊的NPC病人为NPC组，45例健康成人为对照组，两组间性别及年龄无显著差异。NPC病人根据肿瘤有无复发转移又分为两组，均予以^60Coγ射线外照射DT68—80Gy，分别检测放疗前和放疗后(36个月内)及对照组的NK细胞活性及IL-2水平，观察肿瘤复发转移的情况。结果：鼻咽癌病人放疗前、后0-30个月内NK细胞活性及IL-2水平动态观察均明显低于正常对照组(P＜0．05)，至放疗30个月后NK细胞活性及IL-2水平恢复近正常水平。肿瘤复发转移者其NK细胞活性及IL-2水平明显低于无复发转移者(P＜0．05)。30个月内肿瘤复发转移率为85．7％(60/70)。结论：NPC病人免疫功能状况与肿瘤复发转移关系密切。动态观察和评价NK细胞活性及IL-2水平对判断NPC是否复发和转移有一定的指导意义。     

鳞状细胞癌抗原在鼻腔鼻窦鳞癌患者血清中的表达及临床意义

目的 探讨鼻腔鼻窦鳞癌患者血清中鳞状细胞癌抗原(SCC Ag)的表达及其临床意义。方法 对35例鼻腔鼻窦鳞癌、20例鼻内翻性乳头状瘤和30例鼻息肉患者采用微粒子酶免疫法检测血清SCC值,结合临床资料分析该抗原改变的临床意义。结果 鼻腔鼻窦鳞癌、鼻内翻性乳头状瘤、鼻息肉患者SCC阳性率分别为54.29%、35.0%和6.67%,差异有统计学意义(P<0.05); 鼻腔鼻窦鳞癌患者的病理分级及临床分期均与SCC有相关关系(P<0.05)。结论 检测鼻腔鼻窦鳞癌患者血清SCC表达水平对判断病情、临床分期等有一定的临床意义。     

The lack of utility of a tumor marker panel in head and neck carcinoma. Squamous cell carcinoma antigen, carcinoembryonic antigen, lipid-associated sialic acid, and CA-125.

An ideal tumor marker should be sensitive in tumor-bearing patients while having adequate specificity so that controls do not demonstrate the marker. To date, a single circulating marker has not been identified for squamous cell carcinoma of the head and neck. This study evaluates a panel including squamous cell carcinoma radioimmunoassay, lipid-associated sialic acid, carcinoembryonic antigen, and CA-125. In this population of patients with cancer, serum samples from 101 patients and 88 controls were evaluated. The squamous cell carcinoma radioimmunoassay was the most sensitive marker identified (47.5%), while carcinoembryonic antigen level was elevated in 40.6%, lipid-associated sialic acid level in only 16.8%, and CA-125 level in 7.9%. False-positive results were found with all markers, including squamous cell carcinoma radioimmunoassay (18.2%), carcinoembryonic antigen (18.2%), lipid-associated sialic acid (10.2%), and CA-125 (15.9%). Various combinations of markers did not significantly improve either specificity or sensitivity. Available tumor markers are inadequate for diagnostic purposes in patients with squamous cell carcinoma of the head and neck.     

Prognostic value of interleukin-8 and MMP-9 in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is one of the leading causes of cancer related death in China. One of the reasons is the absence of tumor specific prognostic markers. The aim of this study was to examine the prognostic values of interleukin-8 (IL-8) and matrix metalloproteinase-9 (MMP-9) in NPC patients. A total of 99 consecutive NPC patients and 40 healthy controls were recruited for this study. Serum levels of IL-8 and MMP-9 were evaluated in NPC patients who were followed up for 5 years. The serum levels of IL-8 and MMP-9 in NPC patients were significantly higher than those in healthy controls (IL-8 26.3 [2.9–68.0] ng/ml vs. 20.3 [2.3–38.6] ng/ml, P < 0.001; MMP-9 23.5 [3.6–52.1] ng/ml vs. 17.3 [2.6–36.9] ng/ml, P = 0.002), respectively. The serum levels of IL-8 and MMP-9 were positively correlated with the N classification (IL-8, P = 0.041, and MMP-9, P < 0.001, respectively) and clinical stage (IL-8, P = 0.022, and MMP-9, P < 0.001, respectively) in NPC patients. Analysis using the Kaplan–Meier method indicated that patients with high levels of IL-8 or MMP-9 had significantly shorter overall survival (OS) (IL-8, P = 0.012; MMP-9, P < 0.001) and disease-free survival (DFS) (IL-8, P = 0.021; MMP-9, P = 0.003) time than those with low levels of MMP-9 or IL-8. Univariate and multivariate analysis revealed elevated MMP-9 level was an independent predictor of shorter OS and DFS. Both MMP-9 and IL-8 are involved in NPC progression. MMP-9 in serum may be the clinically useful indicator for prognostic evaluation in NPC patients.