dostęp otwarty

Tom 7, Nr 6 (2022)
Praca badawcza (oryginalna)
Opublikowany online: 2022-10-10
Pobierz cytowanie

Tumor-infiltrating lymphocytes and levels of PD-L1 and BRCA protein expression may identify patients with breast cancer with a higher rate of BRCA1 mutations

Polina Damyanova Dimitrova1, Savelina Ljubenova Popovska1, Angel Danchev Yordanov2
Biuletyn Polskiego Towarzystwa Onkologicznego Nowotwory 2022;7(6):411-420.
Afiliacje
  1. Department of General and Clinical Pathology, Medical University-Pleven, Pleven, Bulgaria
  2. Department of Gynaecologic Oncology, Medical University Pleven, Pleven, Bulgaria

dostęp otwarty

Tom 7, Nr 6 (2022)
Artykuły oryginalne / Original articles
Opublikowany online: 2022-10-10

Streszczenie

Introduction.Breast cancer (BC) is a heterogeneous disease, treated as per the predictive role of immunohistoche­mistry (IHC) identifiers as estrogen/progesterone and HER2 receptor proteins. Deeper molecular classification (MC) identifies molecular subtypes according to the gene-expression profiles, with different molecular genetic alterations and biological features, present in the different subtype. An overlap between IHC and MC exists, even if somewhat incomplete. We aimed to identify the overlap between IHC and MC, and identify patients with basal-like subtype of BC. We hypothesized that the rates of tumor expression of breast cancer-related protein 1 (BRCA1), the type of tumor-infiltrating lymphocytes, and the expression of programmed death ligand 1 (PD-L1) by immune cells vary among different subtypes of BC.

Material and methods.Parafin-embedded samples from 100 patients with primary invasive BC were analyzed and expression levels of estrogen and progesterone receptors, HER2 status, and Ki-67 were assessed via IHC, defining four groups – luminal A-like, luminal B-like (LumA, LumB), HER2-positive non-luminal, and triple negative (TN). The pri­mary endpoint of our study was to identify via IHC with CK5/6 and 17 basal-like subtypes of BC amongst others, and to describe specific clinicopathological features together with protein expression of BRCA1 and PD-L1 and tumor-infiltrating lymphocytes, using CD20, CD3, CD4, CD8, and FoxP3.

Results.Basal-like BC were predominantly characterized as triple negative by IHC (p < 0.05) and were more frequently seen among special BC subtypes as compared to no special type (NST), with p = 0.036. Their immune response was represented mostly by high concentration of intratumoral cytotoxic CD8 (+) T-lymphocytes (p < 0.05) and stromal PD-L1-positive immune cells (p = 0.008). In these tumors, absence of expression of BRCA1 protein was more frequent (p < 0.001). Basal-like subtype of BC with absent expression of BRCA1 is associated with poorer <5-year survival (p = 0.001 and p = 0.017, respectively).

Conclusions.The use of IHC can establish basal-like BC, the type of its immune response and possible dysfunction in the BRCA-gene, reflected in the lack of expression in the BRCA-related protein.

Streszczenie

Introduction.Breast cancer (BC) is a heterogeneous disease, treated as per the predictive role of immunohistoche­mistry (IHC) identifiers as estrogen/progesterone and HER2 receptor proteins. Deeper molecular classification (MC) identifies molecular subtypes according to the gene-expression profiles, with different molecular genetic alterations and biological features, present in the different subtype. An overlap between IHC and MC exists, even if somewhat incomplete. We aimed to identify the overlap between IHC and MC, and identify patients with basal-like subtype of BC. We hypothesized that the rates of tumor expression of breast cancer-related protein 1 (BRCA1), the type of tumor-infiltrating lymphocytes, and the expression of programmed death ligand 1 (PD-L1) by immune cells vary among different subtypes of BC.

Material and methods.Parafin-embedded samples from 100 patients with primary invasive BC were analyzed and expression levels of estrogen and progesterone receptors, HER2 status, and Ki-67 were assessed via IHC, defining four groups – luminal A-like, luminal B-like (LumA, LumB), HER2-positive non-luminal, and triple negative (TN). The pri­mary endpoint of our study was to identify via IHC with CK5/6 and 17 basal-like subtypes of BC amongst others, and to describe specific clinicopathological features together with protein expression of BRCA1 and PD-L1 and tumor-infiltrating lymphocytes, using CD20, CD3, CD4, CD8, and FoxP3.

Results.Basal-like BC were predominantly characterized as triple negative by IHC (p < 0.05) and were more frequently seen among special BC subtypes as compared to no special type (NST), with p = 0.036. Their immune response was represented mostly by high concentration of intratumoral cytotoxic CD8 (+) T-lymphocytes (p < 0.05) and stromal PD-L1-positive immune cells (p = 0.008). In these tumors, absence of expression of BRCA1 protein was more frequent (p < 0.001). Basal-like subtype of BC with absent expression of BRCA1 is associated with poorer <5-year survival (p = 0.001 and p = 0.017, respectively).

Conclusions.The use of IHC can establish basal-like BC, the type of its immune response and possible dysfunction in the BRCA-gene, reflected in the lack of expression in the BRCA-related protein.

Pobierz cytowanie

Słowa kluczowe

breast cancer; PD-L1; BRCA1; tumor-infiltrating lymphocytes

Informacje o artykule
Tytuł

Tumor-infiltrating lymphocytes and levels of PD-L1 and BRCA protein expression may identify patients with breast cancer with a higher rate of BRCA1 mutations

Czasopismo

Biuletyn Polskiego Towarzystwa Onkologicznego Nowotwory

Numer

Tom 7, Nr 6 (2022)

Typ artykułu

Praca badawcza (oryginalna)

Strony

411-420

Opublikowany online

2022-10-10

Wyświetlenia strony

3196

Wyświetlenia/pobrania artykułu

96

Rekord bibliograficzny

Biuletyn Polskiego Towarzystwa Onkologicznego Nowotwory 2022;7(6):411-420.

Słowa kluczowe

breast cancer
PD-L1
BRCA1
tumor-infiltrating lymphocytes

Autorzy

Polina Damyanova Dimitrova
Savelina Ljubenova Popovska
Angel Danchev Yordanov

Referencje (36)
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