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CYFRA 21-1 as a biological marker of lung cancer. Evaluation of sensitivity, specificity and prognostic role
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CYFRA 21-l as a Mobgical marker of lung cancer. Evaluation of sensitivity, specificity and progwh role. B. Wicskop*, C. LhmuqeaV, A. Purohit*, R. Stenger*, P. G&s*. G. Pauli+. H. Krehman**, E. f&oh*. * H6pitaux Univecsitains, Pavilion Laennec, Strasbourg, France ** MCGill University, Monlreal. Canada.
rmmuNocnw~m~sntY (rcc) AND BONE mETAsTAsEs 0~ smu ~E~LuNG~AN~ER~L~.
Serum levels of Cyfra 21-1 were measured in 161 lung cancer patients (72 squamous cell, 29 adenocarcinomas, 15 large-cell and 45 small cell), 69 nonmalignant controls (benign pulmonary diseases), 11 non-pulmonary malignancies. In addition to Cyfra 21-1 CEA, NSE and total LDH dosages were performed in lung cancer patients, SCC dosage only in squamous cell carcinoma (SQC) patients; SCC, CEA and NSE dosages were also performed in 35 of the 69 non malignant controls. ROC curve constructed with various cutoff levels of Cyfra 21-1 illustrates the accuracy of serum Cyfra 21-l to predict SQC or other non small cell lung carcinomas. The best compromise between true positive (80%) and false positive (16%) rates was given by the threshold of 2 nglml. At the threshold of 3.3 nglml sensitivity was 70% and specificity 94%. Area under curve was 0.865 for SQC, 0.792 for other NSCLC, 0.653 for small cell lung carcinomas (SCLC). The median (interquartile range) serum Cyfra 21-1, in SQC, other NSCLC and SCLC was respectively 6.0 (2.5-19), 4.3 (2.5-16) and 1.7 (0.98-2.4) @ml. The median (interquattile range) serum Cyfra 21-1 in non malignant controls and non-pulmonary malignancies was 1.0 (0.87~ 1.4) and 3.5 (1.2-14) nglml. Cyfra 21-1 level was found to vary significantly with respect to histological type of lung cancer and with respect to stage of NSCLC. Cyfra 21-l is superior to CEA and SCC in discriminating SQC and to CEA in discriminating other NSCLC from non malignant controls. NSE is superior to Cyfra 21-l in predicting SCLC. Univariate analysis of survival of all NSCLC patients showed significant difference according to performance status, stage, Cyfra 21-1 level, ACE level, LDH. All these variables were included in a Cox’s model. PS, Cyfra 21-1 serum level and stage were the only independent prognostic factors.
The true frequency of bone marrow metastases in SCLC is likely significantly higher than that found using routine procedures. In some series, 35 to 50% of patients classified as limited disease were reclassified as extensive disease after ICC has been performed on bone marrow. However, the limits of detection of ICC are unknown. We evaluated this using bone marrow (BM) from healthy patients artificially mixed with a predetermined proportion of tumor cells (TC). TC were obtained from two SCLC cell lines, NC1 345 and NC1 417. Mononuclear cells were obtained from bone marrow aspirates after centrifugation over Ficoll Hypaque gradient. From each aspirate, different suspensions containing the following ratios of TC:BMcells (BMC) were prepared: O:l, l:l, 1:10, 1:100, 1:1000, 1:lO 000. Suspensions were spun on slides using a cytocentrifuge (0.3m1, l&c/ml). For each sample hematoxylin and eosin (H&E) staining and immunostaining using the ABC procedure (Avidin Biotittylated Complex) were performed. Monoclonal Antibody (MoAb) CAM5.2, an anticytokeratbt. was selected because it stains 95% of both tumor cell lines but no BMC. 9 series from 6 patients were prepared independently. Slides were classified as “metastatic” or not by two readers. The limit of detection of H&E staining was lTC/lOOBMC. In contrast, slides containing one isolated TC among 1,000 BMC could be easily recognized as “metastatic” in 8 (88%) of immunostained slides. It was impossible to conclude in 1 case. It is possible that ICC, when using a MoAb with such a sensitivity, is powerful enough to allow the detection of 1 TC in 10,000 BMC. However, at this concentration the mixing procedure was not reproducible enough to provide significant results. New series are in progress to confirm these results. We conclude that ICC using a CAM5.2 antibody was more sensitive than H&E for detection of bone marrow metastases. It detects 1 :I000 TC and may be able to detect 1:10.000 TC:BMC.
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CYFRA 21-1 AS A NEW MARKER IN LUNG CANCERP.J.SOUQUET.F.HUC,D.GALVAlN,C.H..BOHAS, Y.BARBIER,J.P.BERNARD. Department of Thoracic Oncology .CHLYON SUD 69310 PIERRE BENITE- FRANCE. Cytokeratins are members of the intermediate filament groups of proteinsThey are released into the serum on the death of the cell. CYFRA 21-l is a cytokeratin 19 &agment expressed in simple epithelium as well as in bronchial epithelium tumour cells. The specific detection of this fragment is made with two monoclonal antibodies BM 19-21 and KS 19-l. This study was performed to evaluate of CYFRA 21-1 immunoradiometric assay is useful in the diagnosis and the follow-up in lung cancer. Our study was performed in sera from healthy patients , benignpulmonary disease and lung cancer (Non Small Cell and Small Cell Lung Cancer). The detection limit was been assessed as being 0.08 pg/l. Reproductibilities intra and inter assay were respectively inferior to 3.2.% and 5.4.%. The cut of value used elsewhere is 3.3 g/l A this value the specificity is 85 % and sensitivity 22 % for Small Cell Lung Cancer, and 63 % for Non Small Cell Lung Cancer. The sensitivity for squamous cell carcinoma subtypes is 66 % (better than ECA or NSE).The value of CYFRA 21-1 is also correlated will tumour size In conclusion CYFRA 21-l seems to be the first useful marker for Non Small Cell Lung Cancer and especially for epidermoid type and valuable in monitoring treatment.
HISTOLOGICAL CHARACTERISTICS OF FlBERSRONCHOSCOPfCALLY DIAGNOSED LUNG CANCER IN PATIENTS, 1973-1992. Stefanovski, T et al. Macedonia. The incidence of lung cancer has been steadily increasing and sophisticated methods for its detection are now widely available. In order to learn more about the true incidence of this disease and its various histopathological subtypes, a retrospective study was performed, looking at cases diagnosed by fiberoptic bronchoscopy II 151 patients) between 1973 and 1992. During the first four years of this period (1973-l 9771, only 38 patients were diagnosed with lung cancer while during the period 1989-l 992, over 480 patients were diagnosed. Histopathologic analysis showed the predominant malignant tumor type to be squamous cell cancer (47.7%) followed by small cell carcinoma (24%). Less common cell types included adenocarcinoma (8.9961, metastatic disease (1.8%). large cell undifferentiated carcinoma (15.9%) and carcinoid (0.34%). The predominance of squamous cell carcinoma and the gradual decline in incidence of adenocarcinoma over the period of this study may reflect a different pathogenetic basis.
muutow
Charloux A, Fu LY, Alp& L, Brlsson ML, Small D, Wolkove N. Pauli G, Quoix E, Kreisman H. Jewish General Hospital, McGill University, Montreal, Canada. Hopitaux Universitaires. Strasbourg, France.
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CYFRA 21-l as a Mobgical marker of lung cancer. Evaluation of sensitivity, specificity and progwh role. B. Wicskop*, C. LhmuqeaV, A. Purohit*, R. Stenger*, P. G&s*. G. Pauli+. H. Krehman**, E. f&oh*. * H6pitaux Univecsitains, Pavilion Laennec, Strasbourg, France ** MCGill University, Monlreal. Canada.
rmmuNocnw~m~sntY (rcc) AND BONE mETAsTAsEs 0~ smu ~E~LuNG~AN~ER~L~.
Serum levels of Cyfra 21-1 were measured in 161 lung cancer patients (72 squamous cell, 29 adenocarcinomas, 15 large-cell and 45 small cell), 69 nonmalignant controls (benign pulmonary diseases), 11 non-pulmonary malignancies. In addition to Cyfra 21-1 CEA, NSE and total LDH dosages were performed in lung cancer patients, SCC dosage only in squamous cell carcinoma (SQC) patients; SCC, CEA and NSE dosages were also performed in 35 of the 69 non malignant controls. ROC curve constructed with various cutoff levels of Cyfra 21-1 illustrates the accuracy of serum Cyfra 21-l to predict SQC or other non small cell lung carcinomas. The best compromise between true positive (80%) and false positive (16%) rates was given by the threshold of 2 nglml. At the threshold of 3.3 nglml sensitivity was 70% and specificity 94%. Area under curve was 0.865 for SQC, 0.792 for other NSCLC, 0.653 for small cell lung carcinomas (SCLC). The median (interquartile range) serum Cyfra 21-1, in SQC, other NSCLC and SCLC was respectively 6.0 (2.5-19), 4.3 (2.5-16) and 1.7 (0.98-2.4) @ml. The median (interquattile range) serum Cyfra 21-1 in non malignant controls and non-pulmonary malignancies was 1.0 (0.87~ 1.4) and 3.5 (1.2-14) nglml. Cyfra 21-1 level was found to vary significantly with respect to histological type of lung cancer and with respect to stage of NSCLC. Cyfra 21-l is superior to CEA and SCC in discriminating SQC and to CEA in discriminating other NSCLC from non malignant controls. NSE is superior to Cyfra 21-l in predicting SCLC. Univariate analysis of survival of all NSCLC patients showed significant difference according to performance status, stage, Cyfra 21-1 level, ACE level, LDH. All these variables were included in a Cox’s model. PS, Cyfra 21-1 serum level and stage were the only independent prognostic factors.
The true frequency of bone marrow metastases in SCLC is likely significantly higher than that found using routine procedures. In some series, 35 to 50% of patients classified as limited disease were reclassified as extensive disease after ICC has been performed on bone marrow. However, the limits of detection of ICC are unknown. We evaluated this using bone marrow (BM) from healthy patients artificially mixed with a predetermined proportion of tumor cells (TC). TC were obtained from two SCLC cell lines, NC1 345 and NC1 417. Mononuclear cells were obtained from bone marrow aspirates after centrifugation over Ficoll Hypaque gradient. From each aspirate, different suspensions containing the following ratios of TC:BMcells (BMC) were prepared: O:l, l:l, 1:10, 1:100, 1:1000, 1:lO 000. Suspensions were spun on slides using a cytocentrifuge (0.3m1, l&c/ml). For each sample hematoxylin and eosin (H&E) staining and immunostaining using the ABC procedure (Avidin Biotittylated Complex) were performed. Monoclonal Antibody (MoAb) CAM5.2, an anticytokeratbt. was selected because it stains 95% of both tumor cell lines but no BMC. 9 series from 6 patients were prepared independently. Slides were classified as “metastatic” or not by two readers. The limit of detection of H&E staining was lTC/lOOBMC. In contrast, slides containing one isolated TC among 1,000 BMC could be easily recognized as “metastatic” in 8 (88%) of immunostained slides. It was impossible to conclude in 1 case. It is possible that ICC, when using a MoAb with such a sensitivity, is powerful enough to allow the detection of 1 TC in 10,000 BMC. However, at this concentration the mixing procedure was not reproducible enough to provide significant results. New series are in progress to confirm these results. We conclude that ICC using a CAM5.2 antibody was more sensitive than H&E for detection of bone marrow metastases. It detects 1 :I000 TC and may be able to detect 1:10.000 TC:BMC.
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CYFRA 21-1 AS A NEW MARKER IN LUNG CANCERP.J.SOUQUET.F.HUC,D.GALVAlN,C.H..BOHAS, Y.BARBIER,J.P.BERNARD. Department of Thoracic Oncology .CHLYON SUD 69310 PIERRE BENITE- FRANCE. Cytokeratins are members of the intermediate filament groups of proteinsThey are released into the serum on the death of the cell. CYFRA 21-l is a cytokeratin 19 &agment expressed in simple epithelium as well as in bronchial epithelium tumour cells. The specific detection of this fragment is made with two monoclonal antibodies BM 19-21 and KS 19-l. This study was performed to evaluate of CYFRA 21-1 immunoradiometric assay is useful in the diagnosis and the follow-up in lung cancer. Our study was performed in sera from healthy patients , benignpulmonary disease and lung cancer (Non Small Cell and Small Cell Lung Cancer). The detection limit was been assessed as being 0.08 pg/l. Reproductibilities intra and inter assay were respectively inferior to 3.2.% and 5.4.%. The cut of value used elsewhere is 3.3 g/l A this value the specificity is 85 % and sensitivity 22 % for Small Cell Lung Cancer, and 63 % for Non Small Cell Lung Cancer. The sensitivity for squamous cell carcinoma subtypes is 66 % (better than ECA or NSE).The value of CYFRA 21-1 is also correlated will tumour size In conclusion CYFRA 21-l seems to be the first useful marker for Non Small Cell Lung Cancer and especially for epidermoid type and valuable in monitoring treatment.
HISTOLOGICAL CHARACTERISTICS OF FlBERSRONCHOSCOPfCALLY DIAGNOSED LUNG CANCER IN PATIENTS, 1973-1992. Stefanovski, T et al. Macedonia. The incidence of lung cancer has been steadily increasing and sophisticated methods for its detection are now widely available. In order to learn more about the true incidence of this disease and its various histopathological subtypes, a retrospective study was performed, looking at cases diagnosed by fiberoptic bronchoscopy II 151 patients) between 1973 and 1992. During the first four years of this period (1973-l 9771, only 38 patients were diagnosed with lung cancer while during the period 1989-l 992, over 480 patients were diagnosed. Histopathologic analysis showed the predominant malignant tumor type to be squamous cell cancer (47.7%) followed by small cell carcinoma (24%). Less common cell types included adenocarcinoma (8.9961, metastatic disease (1.8%). large cell undifferentiated carcinoma (15.9%) and carcinoid (0.34%). The predominance of squamous cell carcinoma and the gradual decline in incidence of adenocarcinoma over the period of this study may reflect a different pathogenetic basis.
muutow
Charloux A, Fu LY, Alp& L, Brlsson ML, Small D, Wolkove N. Pauli G, Quoix E, Kreisman H. Jewish General Hospital, McGill University, Montreal, Canada. Hopitaux Universitaires. Strasbourg, France.