TY - JOUR T1 - Cut-off Analysis of HLA-A and HLA-B/C Expression as a Potential Prognosticator of Favorable Survival in Patients With Metastatic Breast Cancer JF - Anticancer Research JO - Anticancer Res SP - 1449 LP - 1454 DO - 10.21873/anticanres.16293 VL - 43 IS - 4 AU - STEFAN STEFANOVIC AU - RALPH WIRTZ AU - MARC SÜTTERLIN AU - UROS KARIC AU - ANDREAS SCHNEEWEISS AU - THOMAS M. DEUTSCH AU - MARKUS WALLWIENER Y1 - 2023/04/01 UR - http://ar.iiarjournals.org/content/43/4/1449.abstract N2 - Background/Aim: Loss of differentiation of breast cancer cells in association with a down-regulated class I human leukocyte antigen (HLA) expression can lead to proliferation unhampered by cytotoxic T lymphocytes, which has been proven to be of prognostic relevance. The objective of this study was to determine the levels of HLA-A and HLA-B/C expression in metastatic breast cancer (MBC) cells and their usefulness for predicting 5-year survival. Materials and Methods: This prospective double-blinded cohort study analyzed patients starting a new line of therapy for MBC. RT-qPCR was used to determine the levels of HLA-A and B/C expression in MBC cells and the mRNA-based tumor intrinsic subtype. Two receiver operating characteristic curves (ROC) were constructed in order to determine whether HLA-A and HLA-B/C expression levels can be used for predicting 5-year survival. Youden J points, and sensitivity and specificity optimized cut-off points were determined for both ROC curves. Results: We enrolled 34 patients. The ROC curve for HLA-B/C had the highest AUC compared to HLA-A (0.55 vs. 0.42). High levels of HLA-A and HLA-B/C expression (40-ΔΔCT of 33.5 and 31.9, respectively) were highly specific (reaching 87.5% for HLA-A and even 100% specificity for HLA-B/C) yet insensitive for five-year survival in our study. Conclusion: High expression of certain class I HLA molecule subtypes by MBCs, in particular high HLA-A or B/C expression by MBC cells seems very specific in predicting the 5-year survival. We determined cut-off values for these HLA molecule clusters with high specificity, which might help identify patients with a favorable prognosis as prognosticators of a 5-year overall survival if their sensitivity is improved in larger prospective cohorts. ER -