Format

Send to:

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2014 May 15;20(10):2773-82. doi: 10.1158/1078-0432.CCR-13-2702. Epub 2014 Mar 19.

In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas.

Author information

  • 1Authors' Affiliations: Departments of Pathology and Medical Oncology, Yale School of Medicine, New Haven, Connecticut; and Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio kurt.schalper@yale.edu.
  • 2Authors' Affiliations: Departments of Pathology and Medical Oncology, Yale School of Medicine, New Haven, Connecticut; and Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio.

Abstract

PURPOSE:

Blockade of the PD-1/PD-L1 axis emerged as a promising new therapeutic option for cancer that has resulted in lasting responses in metastatic renal, lung carcinomas, and melanomas. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway. Measurement of PD-L1 protein is limited by the lack of standardized immunohistochemical methods and variable performance of antibodies. Our goal was to correlate PD-L1 mRNA expression with clinical variables in primary breast carcinomas.

EXPERIMENTAL DESIGN:

The fluorescent RNAscope paired-primer assay was used to quantify in situ PD-L1 mRNA levels in 636 stage I-III breast carcinomas on two sets of tissue microarrays [YTMA128 (n = 238) and YTMA201 (n = 398)]. Tumor-infiltrating lymphocytes (TIL) were assessed by hematoxylin/eosin stain and quantitative fluorescence.

RESULTS:

On YTMA128 and YTMA201, 55.7% and 59.5% of cases showed PD-L1 mRNA expression, respectively. Higher PD-L1 mRNA expression was significantly associated with increased TILs (P = 0.04) but not with other clinical variables. Elevated TILs (scores 2 and 3+) occurred in 16.5% on YTMA128 and 14.8% on YTMA201 and was associated with estrogen receptor-negative status (P = 0.01 on YTMA128 and 0.0001 on YTMA201). PD-L1 mRNA expression was associated with longer recurrence-free survival (log-rank P = 0.01), which remained significant in multivariate analysis including age, tumor size, histologic grade, nodal metastasis, hormone receptor, HER2 status, and the extent of TILs (HR, 0.268; CI, 0.099-0.721; P = 0.009).

CONCLUSIONS:

PD-L1 mRNA expression is identified in nearly 60% of breast tumors and it is associated with increased TILs and improved recurrence-free survival. These observations support the evaluation of PD-1/PD-L1-targeted therapies in breast cancer.

©2014 American Association for Cancer Research.

PMID:
24647569
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk