Prognostic significance of HLA EMR8-5 immunohistochemically analyzed expression in osteosarcoma

Abstract

BackgroundDefects in Human Leukocyte Antigen (HLA) class I antigen expression and/or function in tumor cells have been extensively investigated, because of their potential role in the escape of tumor cells from T cell recognition and destruction. The researchers evaluated HLA class I expression in tumor tissue as a prognostic factor in osteosarcoma patients and as a predictor of their survival. This retrospective cohort study was conducted at the pathology laboratory of Ain Shams University Hospital, and Ain Shams University Specialized Hospital during the period between January 2009 and January 2012.MethodsThe researchers investigated HLA class I expression in primary osteosarcoma by immunohistochemistry using EMR8-5 mAbs. Furthermore, researchers evaluated the correlation between HLA class I expression and the clinicopathological status and outcome in formalin fixed paraffin embedded tissues from thirty six (36) patients with osteosarcoma.ResultsA high expression of HLA class I was detected in 18 (50) % of tumor samples examined; while tumors with low or negative expression represented 9 (25%) cases each. Data indicate that the overall survival rate of patients with tumors highly expressing HLA class I was significantly higher than those with low or negative expression.ConclusionDown-regulation of class I antigen expression is associated with features of aggressive disease and a poorer prognosis. Therefore, it is imperative to identify HLA as a prognostic factor at the time of diagnosis to detect chemotherapy-resistant tumors and to generate a modified treatment regimen.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1159334857109547.

Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: a rationale for T-cell-based immunotherapy

“…Importantly, and despite the limited number of patients, HLA class I expression in primary osteosarcomas correlated with a better disease-free survival, which is consistent with previous results [16, 17]. In addition, we observed that HLA class I expression in metastases was frequently positive, and this was in contrast to Tsukahara et al [17] who reported that HLA class I loss or down-regulation occurred more commonly in metastatic osteosarcoma lesions (7 out of 8 cases; 88%).…”

“…Overall, we observed defects in HLA class I expression in 44% of the osteosarcomas, mainly with a heterogeneous pattern instead of a complete lack of HLA class I. Previous studies have reported a loss or a down-regulation of HLA class I expression in approximately 50–62% of osteosarcomas, using a pan-HLA class I antibody (EMR8-5) and a cut-off of 50% positive tumour cells [16, 17]. In our series, negative or heterogeneous expression of HLA-A molecules was found more frequently compared to the other heavy chains HLA-B/C and β2-microglobulin.…”

Serum C-reactive protein and overall survival of patients with osteosarcoma

“…Conventional factors, such as pathological clinical stages and metastasis, are important predictors of poor clinical outcome of osteosarcoma in clinical practice. Furthermore, a number of less common molecular markers have also shown prognostic roles, such as Mediator of RNA polymerase II transcription subunit 19 (Med19), microRNA-9 (miR-9), and human leukocyte antigen (HLA) class I antigen expressions [25][26][27]. However, these markers are only available following surgery or their measurement is complex, and therefore, they are often not used in clinical practice.…”

Immunotherapy: A New (and Old) Approach to Treatment of Soft Tissue and Bone Sarcomas

“…The loss of HLA I expression was recently shown in 39% of undifferentiated pleomorphic sarcomas, 80% of fibrosarcomas, and 88% of dermatofibrosarcomas . For patients with osteosarcomas and high levels of expression of class I MHC/HLA molecules, compared with patients with no expression, overall survival and event‐free survival significantly improved . Regarding Ewing's sarcoma, loss of HLA expression was shown in 79% of Ewing's tumors .…”