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Objectives: Chosen cutoff for cytokeratin 19 fragment antigen (CYFRA 21-1) as a tumor biomarker considerably influences its diagnostic and prognostic usefulness. The aim of the present study is to determine an optimal cutoff value for diagnostic validity of CYFRA 21-1 by Lumipulse ® technology in patients with suspected cancer and also to determine if CYFRA 21-1 levels provide prognostic value. Methods: A consecutive 284 patients suggestive of malignant disease from six hospitals of Madrid were enrolled in a retrospective design. Optimal CYFRA 21-1 cutoff value was obtained by receiver operating characteristic curve and Youden test. The diagnostic validity was evaluated according to sensitivity, specificity, predictive values and likelihood ratios. The prognostic value of CYFRA 21-1 was checked using multiple logistic regression. Thirty-two diagnostic cancers were confirmed. Results: The most optimal cutoff was 3.15 ng/mL. This cutoff showed a better specificity 93.63% (95% confidence interval [CI], 89.66-96.16), positive predictive value 60.98% (95% CI, 44.54-75.38) and positive likelihood ratio 12.65 (95% CI, 7.64-20.95) than the cutoff recommended by Fujirebio® (1.8 ng/mL) (specificity: 73.71% [95% CI, 67.72-78.95], positive predictive value: 29.79% [95% CI, 21.02-40.23] and positive likelihood ratio 3.43 [95% CI, 2.71-4.35]), improving the current diagnostic accuracy. In multivariate analysis, elevated levels of CYFRA 21-1 (>3.15 ng/mL) was confirmed as an unfavorable prognostic factor. Conclusions: The best cutoff for CYFRA 21-1 obtained was 3.15 ng/mL in patients with suspected cancer. This new cutoff decreases the false positive rate and improves the diagnostic efficacy of CYFRA 21-1 as a tumor marker as well as its association with death events.
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Introducción: El déficit de carnitina palmitoiltransferasa II (CPT-II) se debe a mutaciones en el gen CPT2 y se asocia con 3 fenotipos. La forma adulta o muscular con crisis de mialgia y mioglobinuria es la más frecuente. Los fenotipos infantil y neonatal son multiorgánicos y de mayor gravedad. La mutación común en la forma adulta, p.S113L, no se ha descrito en casos de la variante neonatal. Se presenta un caso de forma adulta con mutaciones que previamente se han asociado a fenotipos diferentes. Paciente y métodos: Paciente de 22 años con episodios recurrentes de calambres musculares y orinas oscuras tras realizar esfuerzos prolongados de moderada intensidad, con una marcada elevación sérica de srm-creatincinasa (8.400 U/l) y mioglobina (2.800 ng/ml) y cuyo tejido muscular no mostró signos de miopatía. La actividad de CPT-II muscular se valoró radioquímicamente y el gen CPT2 se amplificó y secuenció en el secuenciador ABIPrism 310 (Applied Biosystems, Foster City, CA). La mutación p.R151Q se confirmó por reacción en cadena de la polimerasa (PCR)-fragmentos de restricción de longitud polimórfica (RFLP). Resultados: La actividad de CPT-II fue del 16% respecto del valor inferior de referencia. Se identificaron 2 mutaciones en heterocigosis en el gen CPT2: p.S113L y p.R151Q. Discusión: La mutación p.R151Q únicamente se ha descrito en homocigosis y en heterocigosis compuesta (p.R151Q y p.P227L) en formas graves, y previamente no se ha asociado p.S113L a una forma clínica grave, lo que sugiere que la expresión del alelo p.S113L podría compensar los efectos deletéreos de la expresión del alelo p.R151Q, dando lugar al fenotipo moderado observado en la paciente. © 2008 AEBM, AEFA y SEQC. Todos los derechos reservados(AU)
Introduction: Mutations in the CPT2 gene cause carnitine palmitoyltransferase (CPT-II) deficiency, which has been associated with three main phenotypes. The most frequent adult muscular form is characterized by recurrent episodes of myalgia and myoglobinuria. The infantile and neonatal variants are severe, multiorgan diseases. The commonest mutation, in the adult form, pS113L, has not been reported so far in neonatal cases. We report on an adult patient presenting with exercise intolerance who harboured mutations previously associated with diverse phenotypes. Patient and methods: A 22 year-old woman presented with recurrent episodes of muscle cramps and dark urine after prolonged exercise of moderate intensity. She showed elevated serum CK (8400 U/L) and myoglobin (2800 ng/mL) levels. Muscle biopsy did not reveal signs of myopathy. Muscle CPT-II enzyme activity was determined by a radiochemical method. CPT2 gene was amplified and sequenced in an ABIPrism 310 Genetic Analyzer (Applied Biosystems, Foster City, CA). The p.R151Q mutation was confirmed by PCR-RFLP analysis. Results: The activity of CPT-II was decreased (16% of the reference lower limit). Two heterozygous missense mutations were identified in the CPT2 gene: p.S113L and p.R151Q. Discussion: The p.R151Q mutation has been described in homozygous and compound heterozygous (p.R151Q and p.P227L) patients with the severe form. The p.S113L mutation has not been associated with ``severe mutations¿¿. We suggest that expression of the ``benign¿¿ p.S113L allele might counteract the deleterious effects of the p.R151Q allele, which may account for the milder phenotype observed in the patient(AU)
