Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies

Woo Young Sun, Yu Kyung Lee, JaSeung Koo

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background: To date, there are no effective therapeutic targeting agents for triple-negative breast cancer (TNBC), and PD-L1 has presented potential as an effective marker of immunotherapeutic agents. The aim of this study was to evaluate the expression of PD-L1 by three different immunohistochemical antibodies in TNBC. Methods: Interpretation of all three PD-L1 antibodies showed good concordance among three readers (kappa value >0.610) in both cancer cells and immune cells. Using a tissue microarray (TMA) constructed from 218 cases of TNBC, we performed immunohistochemical staining using three of the most popular commercially used PD-L1 monoclonal antibodies (clones 28-8, E1L3N and SP142) in cancer cells and immune cells. Results: Using various cut-off values of previous studies (1, 5, 10 and 50 %), the expression rates in cancer cells were: PD-L1 (E1L3N) (14.7, 14.7, 11.0, 2.3 %), PD-L1 (28-8) (13.3, 12.4, 10.1, 1.8 %), and PD-L1 (SP142) (11.5, 11.0, 6.9, 0.5 %), respectively. At the 5 % cut-off value, the discordance rate among the three antibodies was 6.0-10.6 % and was highest between PD-L1 (SP142) and the other two antibodies. The expression rates in immune cells were PD-L1 (E1L3N) (37.6 %), PD-L1 (28-8) (36.7 %), and PD-L1 (SP142) (19.3 %), and the discordance rate among the three antibodies ranged from 13.8 to 24.8 % and was also highest between PD-L1 (SP142) and the other two antibodies. Among stromal histologic types, higher PD-L1 expression in cancer cells and immune cells was measured in inflammatory-type (p < 0.05). The absence of PD-L1 (28-8) staining in immune cells was associated with shorter disease free survival (DFS) and overall survival (OS) (p = 0.043, and p = 0.021) in univariate analyses, and with shorter OS in multivariate Cox analysis (hazard ratio: 5.429, 95 % CI 1.214-24.28, p = 0.027). Conclusions: PD-L1 detection in cancer cells and immune cells varied by antibody clone. The greatest amount of staining occurred with PD-L1 (E1L3N), followed by PD-L1 (28-8) and PD-L1 (SP142). The concordance rate among monoclonal PD-L1 antibodies was higher between PD-L1 (28-8) and PD-L1 (E1L3N). To determine the gold standard antibody and the most appropriate cut-off value, further study of the clinical trial group treated with PD-L1 inhibitor is necessary.

Original languageEnglish
Article number173
JournalJournal of translational medicine
Volume14
Issue number1
DOIs
Publication statusPublished - 2016 Jun 10

Fingerprint

Triple Negative Breast Neoplasms
Antibodies
Cells
Neoplasms
Staining and Labeling
Clone Cells
Microarrays
Hazards
Disease-Free Survival
Monoclonal Antibodies
Tissue
Multivariate Analysis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

@article{5522928747374b3fa5755150dc20752b,
title = "Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies",
abstract = "Background: To date, there are no effective therapeutic targeting agents for triple-negative breast cancer (TNBC), and PD-L1 has presented potential as an effective marker of immunotherapeutic agents. The aim of this study was to evaluate the expression of PD-L1 by three different immunohistochemical antibodies in TNBC. Methods: Interpretation of all three PD-L1 antibodies showed good concordance among three readers (kappa value >0.610) in both cancer cells and immune cells. Using a tissue microarray (TMA) constructed from 218 cases of TNBC, we performed immunohistochemical staining using three of the most popular commercially used PD-L1 monoclonal antibodies (clones 28-8, E1L3N and SP142) in cancer cells and immune cells. Results: Using various cut-off values of previous studies (1, 5, 10 and 50 {\%}), the expression rates in cancer cells were: PD-L1 (E1L3N) (14.7, 14.7, 11.0, 2.3 {\%}), PD-L1 (28-8) (13.3, 12.4, 10.1, 1.8 {\%}), and PD-L1 (SP142) (11.5, 11.0, 6.9, 0.5 {\%}), respectively. At the 5 {\%} cut-off value, the discordance rate among the three antibodies was 6.0-10.6 {\%} and was highest between PD-L1 (SP142) and the other two antibodies. The expression rates in immune cells were PD-L1 (E1L3N) (37.6 {\%}), PD-L1 (28-8) (36.7 {\%}), and PD-L1 (SP142) (19.3 {\%}), and the discordance rate among the three antibodies ranged from 13.8 to 24.8 {\%} and was also highest between PD-L1 (SP142) and the other two antibodies. Among stromal histologic types, higher PD-L1 expression in cancer cells and immune cells was measured in inflammatory-type (p < 0.05). The absence of PD-L1 (28-8) staining in immune cells was associated with shorter disease free survival (DFS) and overall survival (OS) (p = 0.043, and p = 0.021) in univariate analyses, and with shorter OS in multivariate Cox analysis (hazard ratio: 5.429, 95 {\%} CI 1.214-24.28, p = 0.027). Conclusions: PD-L1 detection in cancer cells and immune cells varied by antibody clone. The greatest amount of staining occurred with PD-L1 (E1L3N), followed by PD-L1 (28-8) and PD-L1 (SP142). The concordance rate among monoclonal PD-L1 antibodies was higher between PD-L1 (28-8) and PD-L1 (E1L3N). To determine the gold standard antibody and the most appropriate cut-off value, further study of the clinical trial group treated with PD-L1 inhibitor is necessary.",
author = "Sun, {Woo Young} and Lee, {Yu Kyung} and JaSeung Koo",
year = "2016",
month = "6",
day = "10",
doi = "10.1186/s12967-016-0925-6",
language = "English",
volume = "14",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central",
number = "1",

}

Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies. / Sun, Woo Young; Lee, Yu Kyung; Koo, JaSeung.

In: Journal of translational medicine, Vol. 14, No. 1, 173, 10.06.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies

AU - Sun, Woo Young

AU - Lee, Yu Kyung

AU - Koo, JaSeung

PY - 2016/6/10

Y1 - 2016/6/10

N2 - Background: To date, there are no effective therapeutic targeting agents for triple-negative breast cancer (TNBC), and PD-L1 has presented potential as an effective marker of immunotherapeutic agents. The aim of this study was to evaluate the expression of PD-L1 by three different immunohistochemical antibodies in TNBC. Methods: Interpretation of all three PD-L1 antibodies showed good concordance among three readers (kappa value >0.610) in both cancer cells and immune cells. Using a tissue microarray (TMA) constructed from 218 cases of TNBC, we performed immunohistochemical staining using three of the most popular commercially used PD-L1 monoclonal antibodies (clones 28-8, E1L3N and SP142) in cancer cells and immune cells. Results: Using various cut-off values of previous studies (1, 5, 10 and 50 %), the expression rates in cancer cells were: PD-L1 (E1L3N) (14.7, 14.7, 11.0, 2.3 %), PD-L1 (28-8) (13.3, 12.4, 10.1, 1.8 %), and PD-L1 (SP142) (11.5, 11.0, 6.9, 0.5 %), respectively. At the 5 % cut-off value, the discordance rate among the three antibodies was 6.0-10.6 % and was highest between PD-L1 (SP142) and the other two antibodies. The expression rates in immune cells were PD-L1 (E1L3N) (37.6 %), PD-L1 (28-8) (36.7 %), and PD-L1 (SP142) (19.3 %), and the discordance rate among the three antibodies ranged from 13.8 to 24.8 % and was also highest between PD-L1 (SP142) and the other two antibodies. Among stromal histologic types, higher PD-L1 expression in cancer cells and immune cells was measured in inflammatory-type (p < 0.05). The absence of PD-L1 (28-8) staining in immune cells was associated with shorter disease free survival (DFS) and overall survival (OS) (p = 0.043, and p = 0.021) in univariate analyses, and with shorter OS in multivariate Cox analysis (hazard ratio: 5.429, 95 % CI 1.214-24.28, p = 0.027). Conclusions: PD-L1 detection in cancer cells and immune cells varied by antibody clone. The greatest amount of staining occurred with PD-L1 (E1L3N), followed by PD-L1 (28-8) and PD-L1 (SP142). The concordance rate among monoclonal PD-L1 antibodies was higher between PD-L1 (28-8) and PD-L1 (E1L3N). To determine the gold standard antibody and the most appropriate cut-off value, further study of the clinical trial group treated with PD-L1 inhibitor is necessary.

AB - Background: To date, there are no effective therapeutic targeting agents for triple-negative breast cancer (TNBC), and PD-L1 has presented potential as an effective marker of immunotherapeutic agents. The aim of this study was to evaluate the expression of PD-L1 by three different immunohistochemical antibodies in TNBC. Methods: Interpretation of all three PD-L1 antibodies showed good concordance among three readers (kappa value >0.610) in both cancer cells and immune cells. Using a tissue microarray (TMA) constructed from 218 cases of TNBC, we performed immunohistochemical staining using three of the most popular commercially used PD-L1 monoclonal antibodies (clones 28-8, E1L3N and SP142) in cancer cells and immune cells. Results: Using various cut-off values of previous studies (1, 5, 10 and 50 %), the expression rates in cancer cells were: PD-L1 (E1L3N) (14.7, 14.7, 11.0, 2.3 %), PD-L1 (28-8) (13.3, 12.4, 10.1, 1.8 %), and PD-L1 (SP142) (11.5, 11.0, 6.9, 0.5 %), respectively. At the 5 % cut-off value, the discordance rate among the three antibodies was 6.0-10.6 % and was highest between PD-L1 (SP142) and the other two antibodies. The expression rates in immune cells were PD-L1 (E1L3N) (37.6 %), PD-L1 (28-8) (36.7 %), and PD-L1 (SP142) (19.3 %), and the discordance rate among the three antibodies ranged from 13.8 to 24.8 % and was also highest between PD-L1 (SP142) and the other two antibodies. Among stromal histologic types, higher PD-L1 expression in cancer cells and immune cells was measured in inflammatory-type (p < 0.05). The absence of PD-L1 (28-8) staining in immune cells was associated with shorter disease free survival (DFS) and overall survival (OS) (p = 0.043, and p = 0.021) in univariate analyses, and with shorter OS in multivariate Cox analysis (hazard ratio: 5.429, 95 % CI 1.214-24.28, p = 0.027). Conclusions: PD-L1 detection in cancer cells and immune cells varied by antibody clone. The greatest amount of staining occurred with PD-L1 (E1L3N), followed by PD-L1 (28-8) and PD-L1 (SP142). The concordance rate among monoclonal PD-L1 antibodies was higher between PD-L1 (28-8) and PD-L1 (E1L3N). To determine the gold standard antibody and the most appropriate cut-off value, further study of the clinical trial group treated with PD-L1 inhibitor is necessary.

UR - http://www.scopus.com/inward/record.url?scp=84973445010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973445010&partnerID=8YFLogxK

U2 - 10.1186/s12967-016-0925-6

DO - 10.1186/s12967-016-0925-6

M3 - Article

C2 - 27286842

AN - SCOPUS:84973445010

VL - 14

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

IS - 1

M1 - 173

ER -