@article {STEFANOVIC1449, author = {STEFAN STEFANOVIC and RALPH WIRTZ and MARC S{\"U}TTERLIN and UROS KARIC and ANDREAS SCHNEEWEISS and THOMAS M. DEUTSCH and MARKUS WALLWIENER}, title = {Cut-off Analysis of HLA-A and HLA-B/C Expression as a Potential Prognosticator of Favorable Survival in Patients With Metastatic Breast Cancer}, volume = {43}, number = {4}, pages = {1449--1454}, year = {2023}, doi = {10.21873/anticanres.16293}, publisher = {International Institute of Anticancer Research}, abstract = {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.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/43/4/1449}, eprint = {https://ar.iiarjournals.org/content/43/4/1449.full.pdf}, journal = {Anticancer Research} }