title: Prognosis in adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia evaluated by uPAR-immunohistochemistry.
abstract: Adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia in humans are highly invasive tumours with poor prognosis. The localisation of urokinase-type plasminogen activator receptor (uPAR) was determined in 66 patients; 60 with adenocarcinomas and six cases with Barrett's oesophagus. uPAR was expressed in nearly all cases of invasive adenocarcinomas by populations of cancer cells, macrophages and myofibroblasts at both the invasion front and the tumour core. In areas with high-grade dysplasia or with Barrett's metaplasia adjacent to the tumour tissue, no uPAR-immunoreactivity was found. High local expression of uPAR, therefore, appears to be a characteristic marker for invasive behaviour in this tumour, suggesting that uPAR's contribution to matrix degradation during invasive growth is a late event in carcinogenesis. Using a scoring system for semiquantitative estimation of uPAR-positivity on immmunohistochemically stained specimens, a significant association was found between poor overall survival and high uPAR-score for cancer cells in the tumour core and for macrophages peripherally at the tumour invasion zone. In multivariate analysis, these two uPAR-scores were confirmed as highly significant prognostic parameters independent of Tumour, Node, Metastasis (TNM)-stage and World Health Organization (WHO) classification. The proteolytic action of these malignant and nonmalignant accessory cells thus seemed to follow two main patterns: one dominated by uPAR positive cancer cells and one by uPAR-positive macrophages. Scoring of uPAR-positivity might be a useful parameter for onset of invasion and prognosis in these adenocarcinomas.
authors.affiliation: The Finsen Laboratory, Copenhagen University Hospital, Copenhagen, Denmark. ole.laerum@gades.uib.no
authors.forename: Ole Didrik
authors.initials: OD
authors.lastname: Laerum
authors.forename: Kjell
authors.initials: K
authors.lastname: Ovrebo
authors.forename: Arne
authors.initials: A
authors.lastname: Skarstein
authors.forename: Ib Jarle
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Warner
authors.initials: W
authors.lastname: Alpízar-Alpízar
authors.forename: Lars
authors.initials: L
authors.lastname: Helgeland
authors.forename: Keld
authors.initials: K
authors.lastname: Danø
authors.forename: Boye Schnack
authors.initials: BS
authors.lastname: Nielsen
authors.forename: Martin
authors.initials: M
authors.lastname: Illemann
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis; D002299:Cardia; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000737:chemistry; D009361:Neoplasm Invasiveness; D011379:Prognosis; D055293:Receptors, Urokinase Plasminogen Activator / Q000032:analysis* / Q000276:immunology; D013274:Stomach Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D055293:Receptors, Urokinase Plasminogen Activator