title: High intratumoural but not peritumoural inflammatory host response is associated with better prognosis in primary resected oesophageal adenocarcinomas.
abstract: The host inflammatory response plays an important role in many solid malignancies. Studies on oesophageal adenocarcinomas (EACs) point towards a beneficial role of pronounced immunoreaction, however, congruent results have yet to be obtained. We analysed 111 primary resected EAC using a tissue microarray containing three cores of the tumour centre and the periphery per case. Overall inflammation was assessed by histomorphology. Tumour infiltrating lymphocytes (TILs) were characterised by immunohistochemistry for CD3, CD8 and FoxP3, and evaluated by image analysis (Aperio ImageScope). High levels of inflammation in the tumour centre, but not the periphery were associated with better patient survival (p = 0.001), similar to high counts of intratumoural FoxP3+, CD3+, CD8+ TILs (p = 0.001; p = 0.027; p = 0.038) and a combination of CD3+/CD8+/FoxP3+ TILs, the latter displaying three different prognostic groups (triple high/mixed/triple low; p=0.003). Intratumoural inflammation [hazard ratio (HR) = 0.432; p = 0.030], FoxP3+ TIL counts (HR = 0.411; p = 0.033) and the combination CD3+/CD8+/FoxP3+ TILs (HR = 0.173; p = 0.006) were also independent prognostic parameters. In summary, both high grade total inflammation and high TIL counts in the tumour centre, but not the tumour periphery, show a beneficial prognostic impact on EAC. This may be a target for novel therapeutic options but also serves as prognostic indicator in these tumours.
authors.affiliation: Institute of Pathology, Department of Clinical Pathology, University of Bern, Switzerland.
authors.forename: Alexandra V
authors.initials: AV
authors.lastname: Stein
authors.affiliation: Institute of Pathology, Department of Clinical Pathology, University of Bern, Switzerland.
authors.forename: Bastian
authors.initials: B
authors.lastname: Dislich
authors.affiliation: Institute of Pathology, Department of Clinical Pathology, University of Bern, Switzerland.
authors.forename: Annika
authors.initials: A
authors.lastname: Blank
authors.affiliation: Institute of Pathology, Department of Clinical Pathology, University of Bern, Switzerland.
authors.forename: Lars
authors.initials: L
authors.lastname: Guldener
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital Bern, University of Bern, Switzerland.
authors.forename: Dino
authors.initials: D
authors.lastname: Kröll
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital Bern, University of Bern, Switzerland.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Seiler
authors.affiliation: Institute of Pathology, Department of Clinical Pathology, University of Bern, Switzerland. Electronic address: rupert.langer@pathology.unibe.ch.
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000175:diagnosis / Q000473:pathology; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
chemical_list: D051858:Forkhead Transcription Factors
keywords: CD3; CD8; FoxP3; Oesophageal adenocarcinoma; inflammation; tumour infiltrating lymphocytes