An autopsied case of pulmonary blastoma with high serum alpha-fetoprotein and carcinoembryonic antigen levels

A 75-year-old male case of a pulmonary blastoma with high serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels is reported. A mass shadow in the right lower lung field was visible on examination of a chest X-ray. Serum AFP and CEA levels were 466.1 ng/ml and 5.8 ng/ml, respectively. The autopsy revealed a pulmonary blastoma composed of malignant epithelial and mesenchymal elements. In the epithelial elements, AFP and CEA producing tumor cells were detected by immunoenzymatic labelling (PAP) methods.     

Alpha-fetoprotein (AFP)-producing ovarian tumor in an elderly woman

Apart from typical yolk sac tumors, ovarian tumors with elevated alfa-fetoprotein (AFP) are uncommon and the differential diagnosis needs to consider the hepatoid pattern of a yolk sac tumor, hepatocellular carcinoma metastatic to the ovary, hepatoid carcinoma, and other epithelial ovarian tumors. We report here an AFP-producing ovarian tumor with uncertain pathological diagnosis, which was extremely responsive to chemotherapy. A 59-year-old Japanese woman presented with lower abdominal distension and was found to have a left ovarian mass on pelvic examination and magnetic resonance imaging (MRI) scan. Laboratory tests showed serum AFP, 73 687 ng/ml; carbohydrate antigen 125 (CA125), 1599 U/ml; and carcinoembryonic antigen (CEA), 13.9 ng/ml. Total hysterectomy with bilateral salpingo-oophorectomy, partial omentectomy, and low anterior resection of the rectum was performed, without any residual macroscopic tumor. Microscopically, the tumor was characterized by a hepatoid carcinomatous component composed of solid sheets of large eosinophilic cells with pleomorphic nuclei. The pathological stage was pT2N0M0. Tumor cells were diffusely immunoreactive for AFP and cytokeratin (CAM5.2), but monoclonal CEA and CA19-9 were focally positive in the cytoplasm, while CA125 was negative. The patient was treated postoperatively with three cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin; with this regimen, serum AFP decreased to 16 ng/ml from 12 600 ng/ml just before the initiation of chemotherapy. The patient received secondary cytoreductive surgery of systemic lymphadenectomy, which revealed no evidence of residual tumor.     

Recent progress in radioimmunodetection for cancer using radio-labeled monoclonal antibodies

The concept of injecting anti-tumor antibodies to localize tumors was first introduced in experimental systems by Pressman (1957). Since then, various trials for tumor detection have been performed using anti-tumor antibodies. In 1970's, the radioimmunodetection of cancer has rapidly developed by the use of radioantibodies to oncofetal proteins such as CEA, AFP and hCG. Recently, there are papers dealing with animal studies of external scanning by the monoclonal antibodies that bind selectively to tumor cells derived from murine teratocarcinoma, human malignant melanoma, human mammary carcinoma and human osteosarcoma. As clinical trials the radiolabeled monoclonal antibodies against CEA or AFP were also used for the radioimmunodetection in patients with CEA or AFP-producing tumors, and the positive rates of the scanning ranged from 40 to 94%. Various related problems are also discussed.     

血清及胆汁肿瘤标志物对梗阻性黄疸的诊断意义

目的:探讨血清和胆汁肿瘤标志物对良恶性疾病致梗阻性黄疸的鉴别诊断意义。方法:64例胆总管结石患者和47例壶腹部周围癌患者检测血清AFP、CEA、CA199、总胆红素（TBil）、谷氨酰胺转移酶（GGT）、碱性磷酸酶（ALP）、白细胞（WBC）。所有患者均行逆行胰胆管造影术（ERCP）并检测胆汁AFP、CEA、CA199。两组患者间的化验数值比较采用独立样本t检验,P＜0.05具有统计学差异。有意义化验采用ROC曲线确立最佳临界值。结果:两组患者性别和年龄比较无差异（P>0.05）。两组间胆汁AFP、总胆红素、谷氨酰胺转移酶、碱性磷酸酶、白细胞数值无明显差异（P>0.05）。和胆总管结石组比较,壶腹部周围癌组患者血清AFP水平明显降低,胆汁CEA、血清CEA、血清CA199明显升高（P＜0.05）。ROC曲线计算血清CEA、胆汁CEA、血清CA199鉴别两种疾病最佳临界值分别为 4.965 ng/ml、77.16 ng/ml、193.2 U/ml。结论:胆汁CEA、血清CEA、血清CA199鉴别诊断壶腹部周围癌和胆总管结石有意义。胆汁CEA曲线下面积最大,对壶腹部周围癌早癌筛查及精确诊断有着一定的意义。     

An autopsy case of a gastric cancer associated with elevated AFP, CEA and CA19-9

A 48-year-old male developed gastric cancer (Borrmann III) with lung and liver metastases. Laboratory examination revealed a markedly elevated AFP (24, 241 ng/ml), CEA (9739.8 ng/ml), and CA-19-9 (726U/ml). Nevertheless, he underwent a subtotal gastrectomy for the hemostasis of a bleeding malignant lesion. Histological examination showed a moderately differentiated adenocarcinoma. A PAP for an AFP and a CEA disclosed positive staining. In addition, An autopsy revealed metastases to the liver and lungs with a positive result of PAP for AFP and CEA. Further, CA19-9 also was confirmed weakly in these same tissues, histochemically. Therefore this gastric cancer was considered an AFP, CEA, and CA19-9-producing tumor. Gastric cancer with 3 elevated tumor markers in the same patient is rare and its mechanism may elucidate the origin of gastric cancer and the resulting differentiation in the foregut.     

Tumor markers in testicular tumors

Serum levels of hCG, AFP, CEA and testosterone were measured in 20 patients with testicular tumors for an evaluation of their clinical significance as tumor markers. HCG was elevated in those with chorional and syncytiotrophoblastic cell tumors, but it was also detected in some cases of embryonal carcinoma and seminoma, suggesting the presence of hCG-producing elements. AFP was exclusively elevated in embryonal and yolk sac tumors. CEA and testosterone were mostly normal in all patients. HCG and AFP fluctuated in good correlation with the clinical course. Thus, hCG and AFP were valuable tumor markers for testicular tumors for the diagnosis of histological type and stage and monitoring the therapeutic effect and prognosis.     

Utility of the serum tumor markers: CYFRA 21.1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC) in squamous cell lung cancer

The aim of this study is to assess the clinical usefulness of serum assays of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CYFRA 21.1 in the diagnosis of squamous cell lung cancer. Sixty patients with squamous cell, and twenty-four patients with nonsquamous cell histology of nonsmall cell lung cancer were enrolled in this study. Serum CEA, SCC, and CYFRA 21.1 levels were obtained by commercially available kits. Upper cutoff levels were 10 ng/ml, 3.5 ng/ml, and 3.5 ng/ml, respectively. In squamous cell lung cancer, percentages and 95% confidence interval (CI) of the patients with elevated levels were as follows: for CEA 23.3% (13-36), for SCC 20.0% (10-32), and for CYFRA 21.1 85.0% (73-93). The positivity rate of CYFRA 21.1 was more significant than CEA and SCC in both squamous and nonsquamous cell lung cancer. None of the markers were significant in differentiating squamous/nonsquamous histology. Only tumor marker CEA was significantly elevated in metastatic squamous cell lung cancer (p=0.004). A novel tumor marker CYFRA 21.1 can be used as a reliable tumor marker in diagnosing squamous cell lung cancer. In addition, CEA has an important role in determining metastatic disease.     

alpha-Fetoprotein (AFP), human chorionic gonadotropin (HCG), and carcinoembryonic antigen (CEA) demonstrated in the immature glands of mediastinal teratocarcinoma: a case report

A 21-year-old man with mediastinal teratocarcinoma showed high levels of serum tumor markers: alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and carcinoembryonic antigen (CEA). After modified VAC chemotherapy (vincristine, dactinomycin, and cyclophosphamide), AFP and HCG levels in the serum were reduced significantly, while serum CEA increased gradually to the level of 6.5 ng/ml. Histopathologic study of the tumor obtained by surgical resection and autopsy revealed teratocarcinoma (a combination of embryonal carcinoma and teratoma). By the indirect immunoperoxidase technique, the antigens AFP, HCG, and CEA were stained in the immature glandular tissues of teratoma. By serial section of the tumor, the antigens tested were found in the same gland of the tumor. In addition, the tumor contained high levels of AFP (17353.8 ng/g.wt.), beta-HCG (beta-HCG) (125.05 ng/g.wt.), and CEA (11.37 ng/g.wt.).     

CEA,AFP, CA125, CA153 and CA199 in Malignant Pleural Effusions Predict the Cause

Determination of the cause of malignant pleural effusions is important for treatment and management,especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause ofmalignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA,AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study.Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusionamong different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma,mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysiswas performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significantdifferences in levels of pleural effusion CEA (P<0.01), AFP (P<0.01), CA153 (P<0.01) and CA199 (P<0.01), butnot CA125 (P>0.05), among the seven groups. Receiver operator characteristic analysis showed that, comparedwith other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lungadenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC:0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%),and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%,specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC:0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%)and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%,specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing differentcauses of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosisand treatment for effusions of unknown primaries.     

Value of five tumor markers (AFP, CEA, hCG, hPL and SP1) in diagnosis and staging of testicular germ cell tumors

Serum levels of AFP, CEA, hCG, hPL and SP1 were measured by specific radioimmunoassays in 111 patients with testicular germ cell tumors. Seminomas, mature teratomas and "pure type" embryonal carcinomas, as well as the latter two types of tumor with seminomatous admixture, do not produce markers unless in advanced stages when they may do so (small amounts of hCP, hPL and SP1). Tumors composed of yolk-sac elements alone or mixed with embryonal carcinoma produce AFP: of syncytiotrophoblastic elements - hCG, hPL or SP1; and teratomas with differentiated structures - CEA. Compound tumors can produce any of the five markers. When present in serum after orchiectomy or lymphadenectomy, the markers are useful both in diagnosis of the tumor elements that metastasized and in staging; whereas their absence does not exclude regional or distant metastases which may contain only marker-negative elements, e.g., due to changes in tumor histology. Measurement of the serum levels of the markers informs about the remaining regional tumor elements or latent metastases and therefore is more useful than immunoperoxidase staining which provides information on the already dissected structures only.     

Application of Joint Detection of AFP,CA19-9, CA125 and CEA in Identification and Diagnosis of Cholangiocarcinoma

Objective: To explore the application of joint detection of serum AFP, CA19-9, CA125 and CEA in identificationand diagnosis of cholangiocarcinoma (CC). Materials and Methods: The levels of serum AFP, CA19-9, CA125and CEA of both 30 patients with CC and 30 patients with hepatocellular carcinoma (HCC) were assessed.Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic effects of single and jointdetection of those 4 kinds of tumor markers for CC. Results: The levels of serum CA19-9, CA125 and CEAin CC patients were higher than that in HCC patients,whereas that of serum AFP was significantly lower s.The area under ROC curve of single detection of serum AFP, CA19-9, CA125 and CEA were 0.05, 0.86, 0.84and 0.83, with the optimal cutoff values of 15.4 ng/ml, 125.1 U/ml, 95.7 U/ml and 25.9 ng/ml, correspondingly,and the percentage correct single diagnosis was <79%. With joint detection, the diagnostic effect of combinedAFP, CA19-9, CA125 and CEA was the highest, with an area under the ROC curve of 0.94 (95%CI 0.88~0.99).Conclusions: Single detection of serum CA19-9, CA125 and EA is not meaningful. The sensitivity, specificity,the rate of correct diagnosis and the area under ROC curve of joint detection of AFP, CA19-9, CA125 and CEAare highest, indicating that the joint detection of these 4 tumor markers is of great importance in the diagnosisof CC.     

Alpha-fetoprotein producing gastric cancer responding to combined chemotherapy with UFT and adriamycin

A case of AFP producing gastric carcinoma with liver metastasis that showed marked response to combined chemotherapy with UFT and Adriamycin (ADM) is reported. A 61-year-old man was admitted because of lassitude and abdominal fullness. An upper GI series and computed tomography revealed gastric cancer (Borrmann III) and multiple liver tumors. He had a remarkably high serum AFP level (90,000 ng/ml) and a high CEA level (270 ng/ml). The presence of AFP in the tumor cells of the biopsy specimen was proved immunohistochemically. He was treated with 600 mg of UFT orally every day and ADM (10 mg, iv, on days 1-4, repeated every 14 days), resulting in marked regression (PR, partial response) of both the primary tumor and liver metastasis on the 33 rd day after the start of treatment, with decreasing of serum levels of AFP and CEA. The patient has been asymptomatic without evidence of recurrence for a follow-up period of more than three months with continuing treatment in our outpatient clinic. UFT-ADM therapy appears to be useful for gastric cancer.     

Correlation Between Nuclear DNA Modal Patterns and Preoperative Plasma Carcinoembryonic Antigen Levels in Lung Cancer Patients

In 51 patients with primary lung carcinoma, correlations betweennuclear deoxyribonucleic acid (DNA) distribution patterns andpreoperative plasma carcinoembryonic antigen (CEA) levels wereinvestigated as nonmorphological, quantitative criteria forpredicting prognosis. Plasma CEA levels were determined withan Abbott enzyme immunoassay kit. The level of 5.0 ng/ml wasconsidered the upper limit of the normal value. Patients whoselung carcinoma had already established tumor stem line cellscarrying near-triploid (3c) or near-hexaploid (6c) DNA had higherpreoperative plasma CEA levels than did patients whose carcinoniasconsisted of diploid (2c), tetraploid (4c) or octaploid (8c)tumor cells. Plasma CEA values higher than 15.0 ng/ml occurredonly in the patients with near-3c or near-6c tumor stem linecells, never in the patients with 2c, 4c or Sc tumor stem cells.These results strongly indicate a distinct correlation betweennuclear DNA modal patterns and preoperative plasma CEA levelsin lung cancer patients.     

Evaluation of interleukin-6, interleukin-10 and human hepatocyte growth factor as tumor markers for hepatocellular carcinoma.

AIM: Serum alpha-fetoprotein (AFP) is the most important tumor marker for hepatocellular carcinoma (HCC). Previous reports indicated that HCC was also associated with increased levels of interleukin (IL)-6, IL-10 and hepatocyte growth factor (HGF). This study investigated the role of these cytokines as tumor markers for HCC. METHOD: A total of 128 adults were prospectively enrolled and categorized into four groups: normal subjects (n=29), chronic hepatitis B or C (n=50), non-HCC tumors (n=23) and HCC (n=26). Serum AFP, IL-6, IL-10 and HGF levels were determined in all subjects. RESULTS: The expression of IL-6 or IL-10 (> or =3 pg/ml), or high level of HGF (>1000 pg/ml) or AFP (>20 ng/ml) was observed in only 0-3% of normal subjects. Patients with HCC more frequently had higher IL-6 and IL-10 levels (p<0.05), whereas HGF levels in HCC patients were not significantly elevated compared to patients with chronic hepatitis or non-HCC tumors. Among patients with low (<20 ng/ml) AFP level, IL-6 or IL-10 expression was significantly associated with the existence of HCC (p<0.05). Patients with large (>5 cm) HCC more often had increased IL-6, IL-10 or AFP levels (p values all <0.05). CONCLUSIONS: Serum levels of IL-6 and IL-10 are frequently elevated in patients with HCC but not in benign liver disease or non-HCC tumors. IL-6 and IL-10 may help identify a subset of HCC patients with low AFP level, and may serve as complementary tumor markers in these patients.     

Determination of optimum cutoff levels of plasma des-gamma-carboxy prothrombin and serum alpha-fetoprotein for the diagnosis of hepatocellular carcinoma using receiver operating characteristic curves.

Optimum cutoff levels for plasma des-gamma-carboxy (abnormal) prothrombin (DCP) and serum alpha-fetoprotein (AFP) were determined by analyzing receiver operating characteristic (ROC) curves to discriminate between hepatocellular carcinoma (HCC) and benign hepatic conditions. Plasma DCP levels in 200 patients with HCC and 197 control patients with benign liver diseases were measured by an enzyme immunoassay with anti-DCP monoclonal antibodies, while serum AFP levels for both groups were measured by radioimmunoassay. From ROC curves and tangential lines with a slope of 1.0, the cutoff levels of DCP and AFP were determined to be 0.11 AU/ml and 150 ng/ml, respectively. Lowered cutoff levels of DCP did not improve the sensitivity, in contrast to the increased sensitivity obtained by lowering the specificity of AFP. The sensitivities and specificities determined in this study were close to the currently used values of 0.1 AU/ml for DCP and 200 ng/ml for AFP, justifying these cutoff levels for the differentiation of benign and malignant liver diseases.     

Soluble interleukin-2 receptors and other markers in primary lung cancer.

Serum levels of soluble interleukin-2 receptors (sIL-2R), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), beta-chorionic gonadotropin (beta-HCG), pregnancy-specific glycoprotein (SP1), and beta 2-microglobulin (beta 2M) were taken in 92 patients with primary lung cancer and 43 controls. The mean value of sIL-2R in the cancer group was twice as high as that of the controls (P less than 0.001) and the highest values were observed in those with small cell carcinoma (SCC) (P less than 0.0001). Of the cancer patients, 51.1% had CEA values higher than the cutoff level of 5 ng/ml. Extended-disease patients had a higher percentage of increased CEA values than those with limited disease. Adenocarcinoma (ADCC) and SCC groups had the highest percentages of increased CEA levels. There was no significant difference between the groups for beta-HCG, AFP, SP1, and beta 2M, and intermarker correlation was not seen. The results suggest that sIL-2R and CEA may be useful in monitoring the extent of disease and possibly indicate the histologic subtype, thus having a bearing on treatment and prognosis.     

肺癌患者血清中癌胚抗原和细胞角蛋白片段19的检测与临床价值

目的 探讨血清癌胚抗原(CEA)和细胞角蛋白片段19( CYFRA21-1)检测对肺癌的诊断价值.方法 采用电化学发光法对102例肺癌患者、78例肺部良性病患者和104例健康人血清进行分析,检测CEA和CYFRA21-1水平.结果 肺癌组患者血清中CEA水平及阳性率[(25.77±15.34) ng/ml,47.1％]均明显高于肺良性病组[(4.67±2.21)ml,7.7％]和健康组[(3.98±3.00)ng/ml,3.8％],差异有统计学意义(P＜0.05).肺癌组患者血清中CYFRA21-1水平及阳性率[(14.08±8.34)ng/ml,62.7％]也同样高于肺良性病组[(3.27±2.87)ml,7.7％]和健康组[(2.69±2.02)ng/ml,3.8％],差异有统计学意义(P＜0.05),而良性病组和健康组间差异无统计学意义(P＞0.05).肺癌组患者经TNM分期后,随着肿瘤分期级别的升高,CEA水平[Ⅱ～Ⅳ期分别为(17.78±8.71)ng/ml、(25.84±7.34)ng/ml和(34.85±6.99) ng/ml]和CYFRA21-1水平[Ⅱ～Ⅳ期分别为(10.05±6.76)ng/ml、(15.93±6.66) ng/ml和(22.78±4.12)ng/ml]也升高.CEA和CYFRA21-1联合检测后,灵敏度增高,特异度降低,准确率基本不变.结论 CEA和CYFRA21-1对肺癌有一定的辅助诊断价值,并且对肺癌的分期有一定诊断价值,联合检测可提高对肺癌的阳性诊断.     

Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP

During the last 6 1/2 years, serum AFP has been determined by radioimmunoassay in 387 patients with germ cell tumors of the gonads and extragonadal sites. The histological appearances of all these neoplasms were carefully reviewed. Highly elevated levels of serum AFP were noted in patients with tumors containing endodermal sinus (yolk sac) tumor elements irrespective of the location of the neoplasm or presence or absence of metastatic disease. There was good correlation between the presence and quantity of endodermal sinus (yolk sac) tumor elements within the primary tumor or its metastases and elevated levels of serum AFP. All patients with tumors composed of pure seminoma or dysgerminoma, and teratoma, had normal serum AFP levels. Slightly elevated levels of serum AFP up to 60 ng/mg (upper limit of normal 20 ng/ml) were noted in a few patients with testicular tumors composed of pure embryonal carcinoma, whereas patients with tumors composed of or containing endodermal sinus (yolk sac) tumor elements had serum AFP levels that could be measured in 100's or 1000's of ng/ml. Serum AFP was elevated only in patients with active disease. Serum AFP was determined in 81 patients with gonadal tumors of non germ cell origin and was normal in all these patients. Serum AFP is a very good tumor marker in patients with germ cell tumors composed of or containing endodermal sinus (yolk sac) tumor, irrespective of their location. Serial serum SFP determinations can be used for diagnostic purposes, for monitoring the results of treatment, and for early detection of metastases and recurrences. Serial serum AFP determination is a useful procedure in all patients with germ cell neoplasms and is highly recommended.     

Plasma CEA levels in small cell lung cancer. Correlation with stage, distribution of metastases, and survival

Plasma CEA levels were determined in 61 patients with small cell lung cancer entering chemotherapy protocols between 1976 and 1980. Five quantitative categories were determined: less than 2.5 ng/ml (the standard normal for Hansen assay); 2.6-5.0 ng/ml (the extended normal for smokers); 5.1-20.0 ml; (the intermediate elevation and the transition for the indirect to the direct assay); 20-100 ng/ml; and greater than 100 ng/ml. Forty-seven percent of patients had levels less than 5 ng/ml and only ten of 61 or 16% had levels greater than 20 ng/ml. There was no clearcut relationship of plasma CEA level to stage of disease, in that 40% of patients with extensive disease (32 patients) had levels less than 5 ng/ml and 45% of patients with limited disease (29 patients) had levels greater than 5 ng/ml. Similarly, there was no relationship of CEA level to site of metastases, although levels greater than 100 ng/ml were always associated with liver metastases. The median survival for each quantitative category was similar, ranging from seven to nine months. The use of sequential determinations of CEA to correlate with tumor response was studied in only eight patients with levels greater than 20 ng/ml and a measurable parameter of disease. The qualitative direction of change of CEA was appropriate in those patients responding to treatment but in three nonresponding patients the direction of CEA change paradoxically decreased. In five patients who developed progressive disease, the plasma CEA level predicted the clinical relapse. CEA as a tumor marker for oat cell carcinoma must be applied in conjunction with other tumor parameters and is meaningful in only a small proportion of the total small cell patient population.     

联合检测EGFR、CEA对恶性胸腔积液的诊断价值

目的:评价联合检测胸腔积液患者的胸水细胞块表皮生长因子受体（epidermal growth factor receptor,EGFR）基因拷贝数,以及胸水、血清CEA水平对良恶性胸腔积液鉴别诊断的价值。方法:应用荧光原位杂交技术（Fish法）检测恶性胸腔积液（n=35）、良性胸腔积液（n=30)组患者胸水细胞块EGFR基因拷贝数水平。采用电化学发光全自动生化分析仪检测胸水及血清中CEA水平,根据受试者工作特性曲线（ROC）选取最佳灵敏性和特异性的点作为临界值,评价CEA及联合检测EGFR基因拷贝数对良恶性胸腔积液的诊断价值。结果:35例恶性胸腔积液完成Fish检测。恶性胸腔积液中15例阴性,20例阳性,阳性率为57.1％。其中13例为EGFR基因高度多体性,7例为EGFR基因扩增。肺腺癌16例中,EGFR基因高度多体性、扩增14例,肺腺癌扩增率为87.5％;肺鳞癌14例中,EGFR基因簇状扩增3例(21.4％),点状扩增3例(21.4％),无扩增8例(57.1％),肺鳞癌扩增率为42.9％。腺癌Fish阳性率(87.5％)高于鳞癌(42.9％）,P<0．01。30例良性胸腔积液中有1例脓胸患者EGFR Fish检测阳性,阳性率为3.3%,余检测结果均阴性。恶性胸腔积液患者胸水及血清CEA分别为（220.9±71.65）ng/ml、(18.11±11.38）ng/ml,显著高于良性胸腔积液组（2.31±1.29)ng/ml、(1.67±1.06）ng/ml,差异有统计学意义（P<0.01）。其中,恶性胸腔积液胸水CEA明显高于血清CEA,而良性胸腔积液组中,胸水CEA与血清CEA无明显差异。肺腺癌所致胸水及血清CEA分别为（441.02±102.65)ng/ml、(32.87±28.66）ng/ml,鳞癌所致胸水及血清CEA分别为（28.75±21.39）ng/ml、（5.99±5.32）ng/ml,腺癌显著高于鳞癌,差异有统计学意义（P<0.01）。比较胸水EGFR、CEA对良恶性胸腔积液诊断的效能,两者之间无明显差异（P=0.453＞0.05）。Spearman相关性分析胸水EGFR同CEA之间存在显著正相关。结论:EGFR在恶性胸腔积液的形成中起重要作用,通过Fish技术检测胸水细胞块EGFR基因拷贝数可行,其敏感性为57.1%。对肺腺癌导致恶性胸腔积液的诊断敏感性为87.5%。CEA（临界值5.0ng/ml）在恶性胸腔积液及血清中显著高于良性,其中胸水CEA检测诊断敏感性为65.7%,而在腺癌中为87.5%,其在胸水及血清中的比值＞1.5有助于恶性胸腔积液的诊断。EGFR基因突变阳性与肿瘤标记物CEA阳性表达呈正相关,尤见于肺腺癌患者,两者联合检测可提高诊断性试验的准确性。