title: Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5 protein in gastric aspirates.
abstract: Symptomatic oesophageal cancer is usually advanced and the prognosis poor. Lethality of symptomatic oesophageal cancer has motivated screening for these diseases earlier in their evolution, but reliable methods for early diagnosis remain elusive. We have demonstrated that dysregulated expression of minichromosome maintenance (MCM) proteins 2-7 is characteristic of early epithelial carcinogenesis, and that these key DNA replication initiation factors can be used as diagnostic markers for cervical and genito-urinary tract cancer. In this study, we investigated whether minichromosome maintenance protein 5 (Mcm5) can be used to detect oesophageal cancer cells in gastric aspirates. Two monoclonal antibodies raised against His-tagged human Mcm5 were used in a time-resolved immunofluorometric assay to measure Mcm5 levels in cells isolated from gastric aspirates of 40 patients undergoing gastroscopy for suspected or known oesophageal carcinoma or symptoms of dyspepsia. The test discriminated with high specificity and sensitivity between patients with and without oesophageal cancer (85% sensitivity (95% confidence interval (CI)=62-97%), 85% specificity (CI=66-96%)), as demonstrated by the large area under the receiver operating characteristics curve (0.93 (95% CI=0.85-0.99)). Elevated levels of Mcm5 in gastric aspirates are highly predictive of oesophageal cancer. This simple test for oesophageal cancer is readily automated with potential applications in primary diagnosis, surveillance and screening.
authors.affiliation: Wolfson Institute for Biomedical Research and Department of Histopathology, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, UK.
authors.forename: G H
authors.initials: GH
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Swinn
authors.forename: A T
authors.initials: AT
authors.lastname: Prevost
authors.forename: P
authors.initials: P
authors.lastname: De Clive-Lowe
authors.forename: I
authors.initials: I
authors.lastname: Halsall
authors.forename: J J
authors.initials: JJ
authors.lastname: Going
authors.forename: C N
authors.initials: CN
authors.lastname: Hales
authors.forename: K
authors.initials: K
authors.lastname: Stoeber
authors.forename: S J
authors.initials: SJ
authors.lastname: Middleton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001331:Automation; D001707:Biopsy, Needle; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000096:biosynthesis*; D002471:Cell Transformation, Neoplastic; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D003937:Diagnosis, Differential; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D005773:Gastroscopy; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D015588:Observer Variation; D029702:Schizosaccharomyces pombe Proteins; D012680:Sensitivity and Specificity; D013270:Stomach
chemical_list: D000911:Antibodies, Monoclonal; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D029702:Schizosaccharomyces pombe Proteins; C085711:mcm5 protein, S pombe