Evaluation of a new tumour marker in patients with non-small-cell lung cancer: Cyfra 21.1

Gaast, Ate van der; Schoenmakers, Christian H.H.; Kok, T. C.; Blijenberg, B. G.; Cornillie, Freddy; Splinter, T. A. W.

doi:10.1038/bjc.1994.95

Cited by 104 publications

(40 citation statements)

References 9 publications

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“…These findings are in agreement with the results reported by Niklinski et al in squamous cell lung cancer (Niklinski et al, 1996). Similar findings in squamous cell lung cancer were also reported by Van der Gaast et al ( Van der Gaast et al, 1994). Currently no other circulating tumour marker is able to provide similar sensitivity for detecting recurrent cancer of the head and neck.…”

Section: Discussionsupporting

confidence: 92%

“…77% of patients with no evidence of disease also had no elevation in the marker level. Previous studies show that Cyfra 21-1 levels drop to below cut-off levels 24 hours after successful operation (Ebert et al, 1994;Van der Gaast et al, 1994;Doweck et al, 1995). According to our findings, re-elevation of the marker had a positive predictive value of 75% (10 cases of recurrence, 2 deaths, 4 NED).…”

Section: Discussionsupporting

confidence: 68%

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The prognostic value of the tumour marker Cyfra 21-1 in carcinoma of head and neck and its role in early detection of recurrent disease

et al. 2000

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Summary This study examines a new tumour marker, Cyfra 21-1, as a prognostic marker in predicting the survival of H&N cancer patients, and its correlation with clinical outcome during prolonged follow up of these patients. The study included 67 patients with primary detection of carcinoma of H&N. The survival of these patients was evaluated in correlation with the disease stage and Cyfra 21-1 levels at initial diagnosis. 38 patients were followed clinically and with serial assays for at least 12 months, or until recurrence was diagnosed. Cyfra 21-1 levels were determined periodically, using an Elisa kit. Patients with Cyfra 21-1 < 1.5 ng ml -1 had a higher survival rate compared to patients with Cyfra 21-1 ≥ 1.5 ng ml -1 (63% vs. 20%, respectively). The risk ratio of Ln(Cyfra 21-1) is 1.62 (P = 0.028). In a Cox regression model that included the disease stage and Ln(Cyfra 21-1), Ln(Cyfra 21-1) was preferred as the main parameter for predicting patients survival. In 83% of the 12 patients with recurrent or residual disease, Cyfra 21-1 was elevated before or during clinical detection of the recurrence. Cyfra 21-1 was found to be a prognostic marker for carcinoma of H&N, unrelated to the stage of the disease. Elevated levels of Cyfra 21-1 without clinical evidence of disease can be attributed to the marker's mean lead-time as compared to the clinical appearance of the disease.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 68%

The prognostic value of the tumour marker Cyfra 21-1 in carcinoma of head and neck and its role in early detection of recurrent disease

et al. 2000

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“…Furthermore, a kit (CYFRA 21-1, Roche Diagnostics) is currently being marketed in some parts of Europe for specific detection of a lung cancer-associated K19 fragment (48,49). The assays used for these measurements have employed antibodies that recognize both the intact and the fragmented forms of K8, K18, and K19.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated Cleavage of Cytokeratin 8/18 Heterotypic Complexes Exposes a Neoepitope in Human Adenocarcinomas

Ditzel¹,

Strik²,

Kobæk-Larsen³

et al. 2002

Journal of Biological Chemistry

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The intermediate filament network in simple glandular epithelial cells predominantly consists of heterotypic complexes of cytokeratin 8 (K8) and cytokeratin 18 (K18). In contrast to other cytokeratins, K8 and K18 are persistently expressed during malignant transformation, but changes in cell morphology are accompanied by alterations in the intermediate filament network. To study molecular changes, K8 and K18 were purified from surgically removed colon cancer and normal epithelia tissues. Western blotting and amino acid sequencing revealed the presence of abundant K8 and K18 fragments, truncated at the N terminus, from cancerous, but not normal, epithelial cells. The fragmentation pattern indicates proteolysis mediated by several enzymes, including trypsin-like enzymes. The cancer-associated forms of K8 and K18 are specifically recognized by the human antibody, COU-1, cloned from the B cells of a cancer patient. We demonstrate that COU-1 recognizes a unique conformational epitope presented only by a complex between K8 and K18. The epitope is revealed after proteolytic removal of the head domain of either K8 or K18. A large panel of recombinant K8 and K18 fragments, deleted N-or C-terminally, allowed for the localization of the COU-1 epitope to the N-terminal part of the rod domains. Using surface plasmon resonance, the affinity of COU-1 for this epitope was determined to be 10 9 M ؊1 , i.e. more than 2 orders of magnitude higher than for intact heterotypic K8/K18 complexes. The cellular distribution of truncated K8/K18 heterotypic complexes in viable adenocarcinomas cells was probed using COU-1 showing small fibrillar structures distinct from those of intact K8/K18 complexes. Previously we demonstrated the binding and subsequent internalization of recombinant Fab COU-1 to live cancer cells. We have thus characterized a cancer neoepitope recognized by the humoral immune system. The results have biological as well as clinical implications.The 10 nm intermediate filaments (IF) 1 provide resilience in response to mechanical stress by forming a stable network attached to specific desmosome cell-cell contacts (1). IF can be classified into groups expressed in higher eukaryotes in a tissue-specific and cell type-restricted pattern (2, 3). In epithelial cells, IFs consist of stoichiometrically equal amounts of type I (smaller and acidic) and type II (larger, neutral, or basic) cytokeratin polypeptides, which form strongly interacting heterodimers (4 -6). Cytokeratin 8 (K8) and cytokeratin 18 (K18), type I and II, respectively, are the major components of IFs of simple or single layer epithelia, such as those of the intestine, the liver, and the breast ducts, although cytokeratin 19 (K19) is also present and forms heterodimers with K8 (2, 5). The assembly of IF involves several association steps where the ␣-helical rod domain of the cytokeratin molecules plays the central role (7-9). The head and the tail domains are not thought to be part of the filamentous backbone but to protrude laterally and contribute to profilame...

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“…Cytokeratin 19 is a major component of the cytoskeleton intermediate filaments of simple epithelium cells and is overexpressed in various carcinomas (Moll et al, 1982). A series of concordant studies showed that CYFRA is very suitable for the diagnosis and the follow-up of non-small-cell lung carcinomas, particularly squamous cell carcinomas (Pujol et al, 1993;Stieber et al, 1993;Van der Gaast et al, 1994). High serum values of CYFRA have also been described in other squamous cell carcinomas and in various adenocarcinomas.…”

mentioning

confidence: 99%

Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions

Salama

Miédougé²,

Rouzaud³

et al. 1998

Br J Cancer

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Summary CYFRA 21-1 assay, measuring cytokeratin 19 fragments, was compared with carcinoembryonic antigen (CEA) assay, as an addition to cytological analysis for the diagnosis of malignant effusions. Both markers were determined with commercial enzyme immunoassays in pleural fluid from 196 patients. Cytological analysis and/or pleural biopsy confirmed the malignant origin of the effusion in 99 patients (76 carcinomas, nine pleural mesotheliomas and 14 non-epithelial malignancies). Effusions were confirmed as benign in 97 patients (33 cardiac failures, 39 infectious diseases -including 12 tuberculosis -and 25 miscellaneous effusions). Both markers were significantly higher in malignant than in benign effusions. All the patients with non-epithelial malignancies presented CYFRA and CEA values lower than the 95% diagnostic specificity thresholds (100 and 6 ng ml-' respectively). The diagnostic sensitivity in the group of carcinomas and mesotheliomas was similar for CYFRA (58.8%) and CEA (64.7%). However, CEA had a significantly higher sensitivity in carcinomas (72.4% vs 55.3%), while CYFRA had a clearly higher sensitivity in mesotheliomas (89.9% vs 0%). Interestingly, 12 out of the 16 malignant effusions with a negative cytology were CEA and/or CYFRA positive. Regarding their high diagnostic sensitivity and their complementarity, CEA and CYFRA appear to be very useful for the diagnosis of malignant pleural effusions when cytology is negative.

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Evaluation of a new tumour marker in patients with non-small-cell lung cancer: Cyfra 21.1

Cited by 104 publications

References 9 publications

The prognostic value of the tumour marker Cyfra 21-1 in carcinoma of head and neck and its role in early detection of recurrent disease

The prognostic value of the tumour marker Cyfra 21-1 in carcinoma of head and neck and its role in early detection of recurrent disease

Cancer-associated Cleavage of Cytokeratin 8/18 Heterotypic Complexes Exposes a Neoepitope in Human Adenocarcinomas

Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions

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