Higher PD-L1 Immunohistochemical Detection Signal in Frozen Compared to Matched Paraffin-Embedded Formalin-Fixed Tissues

Purpose: Response to anti-PD-L1/PD-1 immunotherapy correlates with PD-L1 expression in breast cancer. However, the prevalence of PD-L1 positive breast cancer is variable, which could be due to differences in the population/cohort of patients tested or the preservation/detection technology used. To i...

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Main Authors: Hazem Ghebeh, Fatmah A. Mansour, Dilek Colak, Akram A. Alfuraydi, Amal A. Al-Thubiti, Dorota Monies, Monther Al-Alwan, Taher Al-Tweigeri, Asma Tulbah
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Antibodies
Subjects:
Online Access:https://www.mdpi.com/2073-4468/10/3/24
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author Hazem Ghebeh
Fatmah A. Mansour
Dilek Colak
Akram A. Alfuraydi
Amal A. Al-Thubiti
Dorota Monies
Monther Al-Alwan
Taher Al-Tweigeri
Asma Tulbah
author_facet Hazem Ghebeh
Fatmah A. Mansour
Dilek Colak
Akram A. Alfuraydi
Amal A. Al-Thubiti
Dorota Monies
Monther Al-Alwan
Taher Al-Tweigeri
Asma Tulbah
author_sort Hazem Ghebeh
collection DOAJ
description Purpose: Response to anti-PD-L1/PD-1 immunotherapy correlates with PD-L1 expression in breast cancer. However, the prevalence of PD-L1 positive breast cancer is variable, which could be due to differences in the population/cohort of patients tested or the preservation/detection technology used. To investigate this variability, we examined the effect of two tissue preservation methods on PD-L1 immunohistochemical detection in breast cancer. Methods: We compared PD-L1 expression in patient-matched frozen (FR) and formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer patients. PD-L1 expression was assessed using tumor proportion score (TPS, simply PD-L1 score), and case positivity was determined with PD-L1 score ≥5. Results: In FFPE tissues, PD-L1 was positive in 7–10% of tested patients, depending on the antibody used. In patient-matched FR tissues, the same antibodies showed positive PD-L1 expression in 20–30% of cases. The impact of the antibody tested on the rate of PD-L1 positivity (% of PDL1 positive cases) was minor, as evident in the near perfect concordance between PD-L1 score obtained using the different antibodies whether tested in FR or FFPE tissues. However, there was a systematic drop by an average of 13–20% in the PD-L1 score obtained in FFPE tissues compared to their patient-matched FR tissues. Conclusions: In the tested patient-matched cohort, there was consistently a higher PD-L1 score in FR than FFPE tissues, regardless of the antibody used, demonstrating a significant effect on PD-L1 detection due to the preservation method. These findings should inspire further work to improve the sensitivity of PD-L1 detection and possibly search for more sensitive antibodies in FFPE tissues.
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spelling doaj.art-e671fedb9b4a4539aec0b4ca03702f492023-11-22T01:07:18ZengMDPI AGAntibodies2073-44682021-06-011032410.3390/antib10030024Higher PD-L1 Immunohistochemical Detection Signal in Frozen Compared to Matched Paraffin-Embedded Formalin-Fixed TissuesHazem Ghebeh0Fatmah A. Mansour1Dilek Colak2Akram A. Alfuraydi3Amal A. Al-Thubiti4Dorota Monies5Monther Al-Alwan6Taher Al-Tweigeri7Asma Tulbah8Stem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi ArabiaStem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi ArabiaDepartment of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi ArabiaStem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi ArabiaStem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi ArabiaDepartment of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi ArabiaStem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi ArabiaOncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi ArabiaDepartment of Laboratory Medicine and Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi ArabiaPurpose: Response to anti-PD-L1/PD-1 immunotherapy correlates with PD-L1 expression in breast cancer. However, the prevalence of PD-L1 positive breast cancer is variable, which could be due to differences in the population/cohort of patients tested or the preservation/detection technology used. To investigate this variability, we examined the effect of two tissue preservation methods on PD-L1 immunohistochemical detection in breast cancer. Methods: We compared PD-L1 expression in patient-matched frozen (FR) and formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer patients. PD-L1 expression was assessed using tumor proportion score (TPS, simply PD-L1 score), and case positivity was determined with PD-L1 score ≥5. Results: In FFPE tissues, PD-L1 was positive in 7–10% of tested patients, depending on the antibody used. In patient-matched FR tissues, the same antibodies showed positive PD-L1 expression in 20–30% of cases. The impact of the antibody tested on the rate of PD-L1 positivity (% of PDL1 positive cases) was minor, as evident in the near perfect concordance between PD-L1 score obtained using the different antibodies whether tested in FR or FFPE tissues. However, there was a systematic drop by an average of 13–20% in the PD-L1 score obtained in FFPE tissues compared to their patient-matched FR tissues. Conclusions: In the tested patient-matched cohort, there was consistently a higher PD-L1 score in FR than FFPE tissues, regardless of the antibody used, demonstrating a significant effect on PD-L1 detection due to the preservation method. These findings should inspire further work to improve the sensitivity of PD-L1 detection and possibly search for more sensitive antibodies in FFPE tissues.https://www.mdpi.com/2073-4468/10/3/24PD-L1formalinFFPEfrozenimmunohistochemistrybreast cancer
spellingShingle Hazem Ghebeh
Fatmah A. Mansour
Dilek Colak
Akram A. Alfuraydi
Amal A. Al-Thubiti
Dorota Monies
Monther Al-Alwan
Taher Al-Tweigeri
Asma Tulbah
Higher PD-L1 Immunohistochemical Detection Signal in Frozen Compared to Matched Paraffin-Embedded Formalin-Fixed Tissues
Antibodies
PD-L1
formalin
FFPE
frozen
immunohistochemistry
breast cancer
title Higher PD-L1 Immunohistochemical Detection Signal in Frozen Compared to Matched Paraffin-Embedded Formalin-Fixed Tissues
title_full Higher PD-L1 Immunohistochemical Detection Signal in Frozen Compared to Matched Paraffin-Embedded Formalin-Fixed Tissues
title_fullStr Higher PD-L1 Immunohistochemical Detection Signal in Frozen Compared to Matched Paraffin-Embedded Formalin-Fixed Tissues
title_full_unstemmed Higher PD-L1 Immunohistochemical Detection Signal in Frozen Compared to Matched Paraffin-Embedded Formalin-Fixed Tissues
title_short Higher PD-L1 Immunohistochemical Detection Signal in Frozen Compared to Matched Paraffin-Embedded Formalin-Fixed Tissues
title_sort higher pd l1 immunohistochemical detection signal in frozen compared to matched paraffin embedded formalin fixed tissues
topic PD-L1
formalin
FFPE
frozen
immunohistochemistry
breast cancer
url https://www.mdpi.com/2073-4468/10/3/24
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