HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients.
Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC. Tissue microarrays (TMA) were constructed from esophageal tissue taken from patients at different stages in the cancer progression sequence; normal, esophagitis, Barrett's esophagus (BE), low- and high-grade dysplasia (LGD, HGD) and EAC. HLA-DR expression in tissue epithelium and stroma was assessed by immunohistochemistry. HLA-DR expression increased early in the inflammation to cancer progression sequence; with higher expression detected in esophagitis and BE compared to normal tissue. Patients with low (<50%) HLA-DR expression in the EAC tumor epithelium had significantly worse survival outcomes, compared to those with high expression, in both the tumor core (hazard ratio, HR = 2.178, p = 0.024, n = 70) and leading edge (HR = 2.86, p = 0.013, n = 41). Multivariate analysis demonstrated that low HLA-DR expression in leading edge tumor epithelium was an independent predictor of poor survival, associated with a 2.8-fold increase in disease-associated death (p = 0.023). This study shows that HLA-DR is an independent prognostic marker in EAC tumor epithelium. This may have implications for patient stratification strategies as well as EAC tumor immunology.
Department of Surgery, St. James's Hospital, Trinity Translational Medicine Institute, Dublin 8, Ireland.
Margaret R
MR
Dunne
Department of Surgery, St. James's Hospital, Trinity Translational Medicine Institute, Dublin 8, Ireland.
Adriana J
AJ
Michielsen
Department of Surgery, St. James's Hospital, Trinity Translational Medicine Institute, Dublin 8, Ireland.
Katie E
KE
O'Sullivan
Department of Surgery, St. James's Hospital, Trinity Translational Medicine Institute, Dublin 8, Ireland.
Mary Clare
MC
Cathcart
Department of Surgery, St. James's Hospital, Trinity Translational Medicine Institute, Dublin 8, Ireland.
Ronan
R
Feighery
Department of Histopathology, Trinity College, St. James's Hospital, Dublin 8, Ireland.|Department of Pathology, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
Brendan
B
Doyle
Department of Pathology, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
Jenny A
JA
Watson
Department of Surgery, St. James's Hospital, Trinity Translational Medicine Institute, Dublin 8, Ireland.
Naoimh J
NJ
O'Farrell
Department of Surgery, St. James's Hospital, Trinity Translational Medicine Institute, Dublin 8, Ireland.
Narayanasamy
N
Ravi
Department of Pathology, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
Elaine
E
Kay
Department of Surgery, St. James's Hospital, Trinity Translational Medicine Institute, Dublin 8, Ireland.
John V
JV
Reynolds
Centre for Colorectal Disease & School of Medicine, St. Vincent's University Hospital, University College Dublin, Education and Research Centre, Elm Park, Dublin 4, Ireland.
Elizabeth J
EJ
Ryan
Department of Surgery, St. James's Hospital, Trinity Translational Medicine Institute, Dublin 8, Ireland. osullij4@tcd.ie.
Jacintha
J
O'Sullivan
D000230:Adenocarcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000175:diagnosis / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality* / Q000473:pathology; D004941:Esophagitis / Q000175:diagnosis / Q000473:pathology; D004947:Esophagus / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000175:diagnosis / Q000473:pathology; D011379:Prognosis; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D006684:HLA-DR Antigens
Barrett’s esophagus; Esophageal adenocarcinoma; HLA-DR; Inflammation-associated cancer; Prognostic markers; Survival