Lack of cytoplasmic expression of a new marker programmed cell death ligand-1 in tumor cells is significant

Table 9 Results of the studies of the prognostic and predictive significance of programmed cell death-ligand 1 expression in tumor cells

Ref.	No. of patients BC subtype	Clone of anti-PD-L1 antibody	Staining type; cutoff point; n (%) with expression	Association of PD-L1 expression in TCs with BC characteristics
Mori et al[16], 2017	248, all	Clone E1 L3N (monoclonal rabbit antibody, Cell Signaling Technology, Beverly, MA, United States)	NS; ≥ 1%; three scoring intervals: < 1% - negative (58.5); 1%-49% - weak-positive (26.2); ≥ 50% - strong-positive (15.3)	With tumor G3 (Р = 0.0015), a high Ki67 (Р < 0.0001), a high TILs (Р < 0.0001); Correlations with RFS and OS were absent
Oner et al[17], 2023	50, TNBC	Clone SP263 (rabbit monoclonal antibody, Ventana Clone kit)	Membrane; ≥ 1%; four scoring intervals: ≥ 1% and < 5%; ≥ 5% and < 10%; ≥ 10% and < 20%; ≥ 20%; 25 (50)	With G3 (Р < 0.0001) TCs+ score ≥ 20% were associated with a better DFS and DSS
Shang et al[18], 2022	155, HER2+	Clone SP142 (rabbit monoclonal antibody, Ventana, Shanghai Roche Diagnostic Products Limited Company, Shanghai, China)	Membrane or cytoplasmic; ≥ 1%; continuous scale with 5% step; 62 (40)	No correlation
Çetin et al[19], 2024	85, HER2+	Clone 73-10 (monoclonal antibody, Leica Biosystems, Newcastle, United Kingdom)	Membrane; ≥ 1%; 36 (42.4)	No correlation
Hoffmann et al[20], 2022	127, all	Clone ZR3 (rabbit monoclonal antibody, Cell Marque – Sigma-Aldrich, MO, United States)	Membrane or cytoplasmic; ≥ 1%; 40 (31.5)	with a high TILLs (Р = 0.02) and pCR (Р = 0.02)
Kitano et al[21], 2022	166, all (II-III stage)	antihuman PD-L1 polyclonal antibody (ProScience, Poway, California, United States)	Membrane or cytoplasmic; > 0%; All 62 (34); HR+HER2- (20); HR-HER2+ (32); TNBC (49)	With tumor G3 (Р < 0.0001), TNBC (Р < 0.0001), a high TILs (Р < 0.0001), p53 (Р = 0.0074) and pCR for TNBC (Р = 0.05). Correlations with RFS and OS were absent
Qin et al[22], 2015	870, all	Rabbit primary anti-PD-L1 antibody (Cell Signaling Technology, Beverly, MA, United States)	Membrane; ≥ 5%; All 189 (21.7); Luminal A (11.5); HR+HER2+ (7.7); HR+HER2 (8.6); TNBC (55.9)	With tumor size > 20 mm (Р = 0.002), tumor G3 (Р = 0.013), presence of LVI (Р = 0.015), ER-negative status (Р < 0.001) and PR-negative status (Р < 0.001), TNBC (Р < 0.001) and decreased DFS (Р = 0.012) and OS (Р < 0.001)
Muenst et al[23], 2014	650, all	Rabbit-anti-human PD-L1 polyclonal antibody (Abcam, Cambridge, United Kingdom)	Membrane or cytoplasmic; H-score 0-300 (0–99 - negative/Low expression, and 100–300 - positive expression); All 152 (23.4); Luminal A (12.1); HR+HER2+ (28.8); HR+HER2- (20.4); HR-HER2+ (33.9); TNBC (30.7)	With T3-T4 stages (Р < 0.0001), N2 stage (Р < 0.0001), tumor G3 (Р = 0.0007), ER-negative status (Р = 0.002), HER2-positive status (Р = 0.0237), a high Ki67 (Р = 0.043) and decreased OS (Р < 0.0001)
Li et al[24], 2016	501, all	Clone ab58810 (primary polyclonal anti-PD-L1 antibody, Abcam, Cambridge, United Kingdom)	Membrane or cytoplasmic; H-score 0-300 (0–99 - negative/Low expression, and 100–300 - positive expression); All 231 (46.1); Luminal A (37.0); HR+HER2- (45.8); HR+HER2+ (48.5); HR-HER2+ (57.5); TNBC (58.2)	With tumor G3 (Р = 0.0008), N2-N3 stages (Р = 0.005), ER-negative status (Р = 0.006) and PR-negative status (Р < 0.001), and decreased DFS (Р < 0.001) and OS (Р = 0.002)
Wang et al[25], 2017	443, all	Clone SP142 (Pleasanton, CA, United States)	NS; H-score 0-300; All 73 (16.5); Luminal A (12); Luminal B (21); HR-HER2+ (9); TNBC (31)	With tumor G3 (Р = 0.001), ER-negative status (Р = 0.005) and PR-negative status (Р = 0.002), a high TILs (Р < 0.05). Correlations with RFS and OS were absent (Р > 0.05)
Parvathareddy et al[26], 2021	1003, TNBC	Clone E1 L3N (Cell Signaling Technology, Danvers, MA, United States)	Membrane and cytoplasmic but only membrane was assessed; ≥ 5%; 329 (32.8)	With younger age (Р = 0.0432), tumor G3 (Р = 0.0025), ER-negative status (Р < 0.0001), PR-negative status (Р = 0.0001), TNBC (Р = 0.0062) and a high Ki67 (Р < 0.0001). Correlations with RFS and OS were absent (Р > 0.05)
Guo et al[27], 2020	341, all	Clone 22C3 (Dako North America Inc., Carpinteria, CA, United States)	Membrane; ≥ 1%; All 24 (10); HR+ (9); HER2+ (16); TNBC (10)	with tumor G3 (Р < 0.0001), PR-negative status (Р = 0.0125), a high TILs (Р < 0.0001)
Chu et al[28], 2022	132, TNBC	Clone SP142 (Ventana Medical Systems)	Membrane; ≥ 1%; All 36 (27.3); ≥ 10% (2.3)	Correlations with RFS and OS were absent
Ni et al[29], 2022	1752, all	Clone SP142 (rabbit monoclonal primary antibody, Ventana Medical Systems Inc.)	Membrane; ≥ 1%; 173 (10.1)	With ER-negative status, PR-negative status, HER-positive status, TNBC, a high Ki67, a high TILs and PD-L1-positive ICs; Correlations with DSS, RFS and OS were absent

BC: Breast cancer; DSS: Disease-specific survival; ER: Estrogen receptor; HER2: Human epidermal growth factor receptor 2; HR: Hormone receptor; H-score: Histo-score; LVI: Lymphovascular invasion; NS: Not specified; OS: Overall survival; pCR: Pathologic complete response; PD-L1: Programmed cell death ligand 1; PR: Progesterone receptor; RFS: Relapse-free survival; TCs: Tumor calls; TILs: Tumor infiltrating lymphocytes; TNBC: Triple negative breast cancer.