HLA‐DR expression is associated with better prognosis in sporadic Australian clinicopathological Stage C colorectal cancers

Abstract

Predicting patient outcome for colorectal carcinoma (CRC) with lymph node but not distant metastases remains challenging. Various prognostic markers have been identified including microsatellite instability (MSI) and possibly expression of the MHC Class II protein, HLA-DR. About 15% of sporadic CRC exhibits MSI associated with methylation of the DNA mismatch repair gene hMLH1 promoter. In addition, a significant proportion of unselected CRC demonstrates expression of HLA-DR. We sought to examine the relationship between HLA-DR expression, MSI status and prognosis in sporadic Australian Clinicopathological (ACP) Stage C CRC. Two hundred seventy consecutive patients with sporadic ACP Stage C CRC were treated at Concord Repatriation General Hospital between 1986 and 1992. None of these patients received adjuvant chemotherapy and all were followed for a minimum of 5 years or until death. DNA was extracted from paraffin sections and MSI status determined by PCR. HLA-DR expression was determined immunohistochemically using an antibody against the HLA-DR a chain. MSI status could be assigned in 235 cases: 176 CRCs (74.9%) were microsatellite stable, whereas 23 (9.8%) had high levels of MSI (MSI-H) and 36 (15.3%) had low levels of MSI (MSI-L). HLA-DR expression by CRC cells was seen in 148 (60.1%) cases and correlated with the presence of tumor-infiltrating lymphocytes (p 5 0.0005) and peritumoral lymphocytes (p 5 0.003), but not other clinicopathological features or MSI status. HLA-DR-positive CRCs were strongly associated with better patient outcome (p < 0.0001). ' 2009 UICC

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

“…In this context, it is noteworthy that HLA class II antigen expression in CRC is closely related to the high-level microsatellite instability (MSI-H) phenotype 33,39 underlining that a precise molecular classification is required to obtain reliable information about the frequency of HLA class II antigen expression in defined tumor subtypes. 37 This conclusion is further supported by the observation in head and neck cancers, where HLA class II antigen expression is related to human papillomavirus infection of the lesions. 40 Altered constitutive and IFNg inducible HLA class II antigen expression in cancer cells…”

“…For example, the frequency of HLA class II positivity in colorectal carcinoma (CRC) reported in the literature varied between 21 and 55% depending on the study. [34][35][36][37][38] These different results may reflect differences in the methodology and antibodies used, in the characteristics of the patients' population included in the studies and in the molecular pathogenesis of the disease. In this context, it is noteworthy that HLA class II antigen expression in CRC is closely related to the high-level microsatellite instability (MSI-H) phenotype 33,39 underlining that a precise molecular classification is required to obtain reliable information about the frequency of HLA class II antigen expression in defined tumor subtypes.…”

“…Immunohistochemically detectable HLA class II antigen expression was associated with a better prognostic outcome of CRC patients in some studies, 36 but not associated with tumor grade, stage and survival in other studies. 37,80 A positive prognostic effect of HLA class II antigen expression in CRC may reflect the increased T-cell infiltration which is one of the strongest favorable prognostic biomarkers in CRC. 81 Consequently, high levels of IFNg might induce HLA class II antigen expression in densely T cell-infiltrated tumors, which has a good prognosis.…”

Invasive front of colorectal cancer: Dynamic interface ofpro-/anti-tumor factors

“…Recently, HLA-DR www.wjgnet.com Zlobec I et al . The invasive front of colorectal cancer expressed constitutively on antigen-presenting cells such as dendritic cells and macrophages has also been found to correlate with the presence of TILs and PTLs as well as improved patient outcome [85] .…”

IL-10: Master Switch from Tumor-Promoting Inflammation to Antitumor Immunity

“…1). In human tumors, expression of MHC molecules is correlated with improved prognosis for the patients (39). Consequently, PEG-IL-10 also led to a dramatic surge of tumor cell-specific, intratumoral CD8 þ T cells.…”