Dunne Margaret R, Michielsen Adriana J, O'Sullivan Katie E, Cathcart Mary Clare, Feighery Ronan, Doyle Brendan, Watson Jenny A, O'Farrell Naoimh J, Ravi Narayanasamy, Kay Elaine, Reynolds John V, Ryan Elizabeth J, O'Sullivan Jacintha
Department of Surgery, St. James's Hospital, Trinity Translational Medicine Institute, Dublin 8, Ireland.
Department of Histopathology, Trinity College, St. James's Hospital, Dublin 8, Ireland.
Cancer Immunol Immunother. 2017 Jul;66(7):841-850. doi: 10.1007/s00262-017-1983-1. Epub 2017 Mar 18.
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.
食管腺癌（EAC）是一种侵袭性癌症，预后较差，在西方世界其发病率正在迅速上升。免疫标志物的检测已显示在越来越多的癌症中具有预后意义，但对于EAC是否如此尚未得到评估。本研究旨在描述在从炎症到癌症进展序列的整个过程中食管中HLA-DR的表达特征，并评估HLA-DR表达在EAC中的预后意义。组织微阵列（TMA）由取自癌症进展序列不同阶段患者的食管组织构建而成；包括正常组织、食管炎、巴雷特食管（BE）、低级别和高级别异型增生（LGD、HGD）以及EAC。通过免疫组织化学评估组织上皮和基质中HLA-DR的表达。HLA-DR表达在炎症到癌症进展序列的早期增加；与正常组织相比，食管炎和BE中检测到更高的表达。在EAC肿瘤上皮中HLA-DR表达低（<50%）的患者与高表达患者相比，在肿瘤核心（风险比，HR = 2.178，p = 0.024，n = 70）和前沿（HR = 2.86，p = 0.013，n = 41）的生存结果均明显更差。多变量分析表明，前沿肿瘤上皮中HLA-DR低表达是生存不良的独立预测因素，与疾病相关死亡增加2.8倍相关（p = 0.023）。本研究表明，HLA-DR是EAC肿瘤上皮中的独立预后标志物。这可能对患者分层策略以及EAC肿瘤免疫学具有意义。
