PD1 protein expression in tumor infiltrated lymphocytes rather than PDL1 in tumor cells predicts survival in triple-negative breast cancer

Abstract

To determine PD1/PDL1 expression status in triple-negative breast cancer (TNBC) at both protein and mRNA levels, and to analyze the relationship between their expression and clinical parameters of the TNBC patients. Immunohistochemistry and RNAscope were used to semi quantitively evaluate PD1/PDL1 protein and mRNA expression in 195 TNBC cases on tissue microarrays. Tumor infiltrating lymphocyte (TILs) abundance was assessed using hematoxylin-eosin staining. Both tumor cells and TILs expressed PDL1. PDL1 protein and mRNA positivity was 6.7% and 74.4% respectively in tumor cells, and 31.3% and 50.9% respectively in TILs. PDL1 protein and mRNA expressions had no significant association with patient prognosis. PD1 protein was only detected in TILs (70.3% positivity). PD1 protein expression was significantly related to PDL1 expression, higher TIL abundance, Ki-67 index, basal-like subtypes, and distant metastasis. Furthermore, it was significantly associated with longer disease free survival (P<0.001) and overall survival (P = 0.004). There was no significant association between PD1 mRNA expression and clinicopathological characteristics. PD1/PDL1 protein and mRNA expressions were inconsistent (kappa = 0.705 and 0.061, respectively). PD1 protein expression in TILs, but not PDL1 in tumor cells, was a favorable prognostic factor in TNBC. PD1/PDL1 mRNA and protein expressions were inconsistent.

Programmed death‐ligand 1 gene expression is a prognostic marker in early breast cancer and provides additional prognostic value to 21‐gene and 70‐gene signatures in estrogen receptor‐positive disease

“…We have previously shown that PD‐L1 gene expression is associated with prolonged DFS and OS (Matikas et al , 2019b). In the present study, we confirm that PD‐L1 gene expression is correlated with improved outcomes, while we also demonstrate a significant correlation between PD‐L1 mRNA and protein expression, helping to clarify currently available inconsistent studies that have reported high (Guo et al , 2016; Kim et al , 2017), moderate, or low protein–mRNA correlation (Ali et al , 2015; Ren et al , 2018). PD‐L1 mRNA can thus be a promising and reliable prognostic marker compared with current IHC methods but with unclear—up until now—clinical validity and utility.…”

Potential prognostic value of PD-L1 and FOXP3 as predictors of relapse in breast cancer

“…[1] When evaluated in 136 cases of IDC (NST) in the current study, we found positive expression of PDL1 in 58.8% of cases. Our figure for PDL1 was concor-dant to that reported by Baptista et al (2016), higher than Muenst et al (2014) who reported 23.4%, and much higher than Ren et al (2018) who found it to be 6.7%. [12][13][14] On the other hand, Beckers et al (2016) reported a much higher percentage (64%) but their study included only triple-negative breast cancer cases that may explain this high difference with ours.…”

“…Our figure for PDL1 was concor-dant to that reported by Baptista et al (2016), higher than Muenst et al (2014) who reported 23.4%, and much higher than Ren et al (2018) who found it to be 6.7%. [12][13][14] On the other hand, Beckers et al (2016) reported a much higher percentage (64%) but their study included only triple-negative breast cancer cases that may explain this high difference with ours. [15] Considering the prognostic role of PDL1, we found a significant correlation of PD L1 with two poor prognostic parameters which are high proliferative index and advanced stage.…”

“…The larger number of cases in these studies could help the achievement of statistically significant level than ours. [10,13,16,17] In another view, Ren et al (2018) and Noske et al (2019) found no association between PD L1 expression and clinical outcome. [14,18] On ) found upregulation of PDL1 mRNA or protein in breast cancer to be correlated with better survival due to strong cytotoxic local immune response.…”

Integrative analysis of PD‐L1 DNA status, mRNA status and protein status, and their clinicopathological correlation, in diffuse large B‐cell lymphoma

“…A cut‐off of ≥1 was considered to be statistically significant. Low expression was defined as a score of 0, and high expression was defined as a score of ≥1 …”