Browsing by Author "Wirtz, Ralph (23098919300)"

Background/Aim: The loss of breast cancer cell differentiation during metastatic progression leads to a down-regulation of class 1 human leukocyte antigen (HLA) expression, which in turn hinders cytotoxic T lymphocytes from effectively preventing tumor cell proliferation. Consequently, one would expect that decreased HLA expression would correlate with decreased 5-year survival. However, estrogen receptor alpha (ESR1) is known to be positively associated with overall survival. The study aimed to determine the expression levels of HLA-A, HLA-B/C, and ESR1 and to assess their influence on distant disease-free survival (DDFS). Materials and Methods: This retrospective subgroup analysis of the initial prospective, single-center, double-blind cohort study included a total of 34 patients who underwent a new treatment line for metastatic breast cancer (MBC). The MBC cells were examined using RT-qPCR. Results: The acquired data and the subsequent survival and ROC analyses indicated a positive association of reduced expression of HLA-A and HLA-B/C with DDFS. A statistically significant association of ESR1 with DDFS could not be shown. Conclusion: A potential positive association between reduced expression of HLA-A and HLA-B/C and DDFS is observed. This contrasts with the generally observed association between HLA expression loss and poor prognosis, as reported in previous protein-based studies. In metastatic settings, reduced expression of particular HLA subsets, measured at the mRNA level, might have a protective effect against disease progression. ©2025 The Author(s).

Background/Aim: The loss of breast cancer cell differentiation during metastatic progression leads to a down-regulation of class 1 human leukocyte antigen (HLA) expression, which in turn hinders cytotoxic T lymphocytes from effectively preventing tumor cell proliferation. Consequently, one would expect that decreased HLA expression would correlate with decreased 5-year survival. However, estrogen receptor alpha (ESR1) is known to be positively associated with overall survival. The study aimed to determine the expression levels of HLA-A, HLA-B/C, and ESR1 and to assess their influence on distant disease-free survival (DDFS). Materials and Methods: This retrospective subgroup analysis of the initial prospective, single-center, double-blind cohort study included a total of 34 patients who underwent a new treatment line for metastatic breast cancer (MBC). The MBC cells were examined using RT-qPCR. Results: The acquired data and the subsequent survival and ROC analyses indicated a positive association of reduced expression of HLA-A and HLA-B/C with DDFS. A statistically significant association of ESR1 with DDFS could not be shown. Conclusion: A potential positive association between reduced expression of HLA-A and HLA-B/C and DDFS is observed. This contrasts with the generally observed association between HLA expression loss and poor prognosis, as reported in previous protein-based studies. In metastatic settings, reduced expression of particular HLA subsets, measured at the mRNA level, might have a protective effect against disease progression. ©2025 The Author(s).

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. © 2023 International Institute of Anticancer Research. All rights reserved.

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. © 2023 International Institute of Anticancer Research. All rights reserved.