Balázs Ács1, Lilla Madaras2, Anna-Mária Tőkés3, Attila Kristóf Kovács4, Erzsébet Kovács5, Magdolna Ozsvári-Vidákovich6, Ádám Karászi7, Ede Birtalan8, Magdolna Dank9, Attila Marcell Szász10, Janina Kulka11. 1. 2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: acs.balazs.se@gmail.com. 2. 2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: madaras.lilla@med.semmelweis-univ.hu. 3. MTA-SE Tumor Progression Research Group, 2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: tokesa1972@yahoo.co.uk. 4. 2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: kovacs.attila@med.semmelweis-univ.hu. 5. 2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: azumahne@gmail.com. 6. 2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: magdus.vidak@gmail.com. 7. 2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: adam.karaszi@gmail.com. 8. Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 36 Szigony utca, Budapest, 1083, Hungary. Electronic address: birtalanede@gmail.com. 9. Cancer Center, Semmelweis University, Tömő utca 25-29, Budapest, 1083, Hungary. Electronic address: magdolna.dank@gmail.com. 10. 2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary; Cancer Center, Semmelweis University, Tömő utca 25-29, Budapest, 1083, Hungary. Electronic address: cac@korb2.sote.hu. 11. 2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: kulka.janina@med.semmelweis-univ.hu.
Abstract
PURPOSE: We aimed to compare the immunohistochemical expression of PD-1, PD-L1 and CTLA-4 of pregnancy-related breast cancer (PRBC) and early onset non-PRBC (YWBC), and their prognosis prediction potential was correlated to that of conventional clinicopathological factors. METHODS: Twenty-one PRBC cases were paired with 21 YWBC in this matched case-control study. Immune-checkpoint markers (ICM) were evaluated with immunohistochemistry (IHC) on whole slides using the following antibodies: PD-1 (NAT-105), PD-L1 (28-8) and CTLA-4 (F-8). IHC score was defined as the percentage of positive cells, assessed separately among tumor cells, intratumoral lymphocytes and peritumoral lymphocytes. RESULTS: The optimal threshold of PD-L1 expression of tumor cells occurred at 10% for overall survival (OS, AUC = 0.847, p = 0.009), and at 1% for disease-free survival (DFS, AUC = 0.795, p = 0.010). For PD-L1 expression on intratumoral lymphocytes, the optimal cut-off was 1% (AUC = 0.763, p = 0.048). Considering PD-1, PD-L1 and CTLA-4 expression, no significant difference occurred between PRBC and YWBC (p > 0.05 for all comparisons). PD-1, PD-L1 expressed on peritumoral lymphocytes and CTLA-4 failed, but PD-L1 expressed on tumor cells and on intratumoral lymphocytes was suitable to distinguish patient cohorts with different OS and DFS (p ≤ 0.011 for all comparisons). Higher PD-L1 expression was associated with poor prognosis. PD-L1 expressed on tumor cells represented an independent association with OS (p = 0.023) and DFS (p = 0.032). CONCLUSIONS: Our results suggest that PRBC and YWBC do not differ in the expression of PD-1, PD-L1 and CTLA-4. However, our findings emphasize the relevance of PD-L1 expression in early-onset breast cancer, as an independent negative predictor of prognosis.
PURPOSE: We aimed to compare the immunohistochemical expression of PD-1, PD-L1 and CTLA-4 of pregnancy-related breast cancer (PRBC) and early onset non-PRBC (YWBC), and their prognosis prediction potential was correlated to that of conventional clinicopathological factors. METHODS: Twenty-one PRBC cases were paired with 21 YWBC in this matched case-control study. Immune-checkpoint markers (ICM) were evaluated with immunohistochemistry (IHC) on whole slides using the following antibodies: PD-1 (NAT-105), PD-L1 (28-8) and CTLA-4 (F-8). IHC score was defined as the percentage of positive cells, assessed separately among tumor cells, intratumoral lymphocytes and peritumoral lymphocytes. RESULTS: The optimal threshold of PD-L1 expression of tumor cells occurred at 10% for overall survival (OS, AUC = 0.847, p = 0.009), and at 1% for disease-free survival (DFS, AUC = 0.795, p = 0.010). For PD-L1 expression on intratumoral lymphocytes, the optimal cut-off was 1% (AUC = 0.763, p = 0.048). Considering PD-1, PD-L1 and CTLA-4 expression, no significant difference occurred between PRBC and YWBC (p > 0.05 for all comparisons). PD-1, PD-L1 expressed on peritumoral lymphocytes and CTLA-4 failed, but PD-L1 expressed on tumor cells and on intratumoral lymphocytes was suitable to distinguish patient cohorts with different OS and DFS (p ≤ 0.011 for all comparisons). Higher PD-L1 expression was associated with poor prognosis. PD-L1 expressed on tumor cells represented an independent association with OS (p = 0.023) and DFS (p = 0.032). CONCLUSIONS: Our results suggest that PRBC and YWBC do not differ in the expression of PD-1, PD-L1 and CTLA-4. However, our findings emphasize the relevance of PD-L1 expression in early-onset breast cancer, as an independent negative predictor of prognosis.
Authors: Cinzia Solinas; Soizic Garaud; Pushpamali De Silva; Anaïs Boisson; Gert Van den Eynden; Alexandre de Wind; Paolo Risso; Joel Rodrigues Vitória; François Richard; Edoardo Migliori; Grégory Noël; Hugues Duvillier; Ligia Craciun; Isabelle Veys; Ahmad Awada; Vincent Detours; Denis Larsimont; Martine Piccart-Gebhart; Karen Willard-Gallo Journal: Front Immunol Date: 2017-10-30 Impact factor: 7.561