Endocrine response and resistance in breast cancer: a role for the transcription factor Fos |
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Authors: | JM Gee PC Willsher FS Kenny JF Robertson SE Pinder IO Ellis RI Nicholson |
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Affiliation: | Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Denmark. |
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Abstract: | The concentration of the tumor marker CA 19-9 is influenced by the patient's secretor status and Lewis genotype. The aim of this study was to establish novel reference intervals for CA 19-9 in serum based on secretor and Lewis genotypes, to investigate the biological variation of CA 19-9, and to evaluate the utility of Lewis and secretor genotyping on a group of individuals with serologically defined Lewis phenotypes. CA 19-9 was measured in serum of 500 healthy individuals. Secretor and Lewis genotypes were determined by sequencing and PCR-cleavage methods. Significant differences were found between subgroups with different Lewis and secretor genotypes. Genotype-based reference intervals for CA 19-9 are presented. The upper reference limit for all individuals was 28.7 kilounits/L; for secretors and nonsecretors, the upper reference limits were 12.4 and 61.2 kilounits/L, respectively. The analytical imprecision (CVA) was 9.8%, the within-subject variability (CVI) was 15.8%, and the between-subject variability (CVG) was 102.2%. Good agreement was found between Lewis and secretor genotyping and conventional blood grouping. Genotype-based reference intervals may be a way to increase the clinical utility of CA 19-9. On the basis of the calculation of a critical difference for sequential values (significant at P =0.05) of 51.5%, a 40-50% change in marker concentration is suggested as the limit for significant change when the marker is used for follow up. PCR-based genotyping is a reliable method for secretor and Lewis histo-blood grouping. |
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