Abstract
High tumour-infiltrating lymphocytes correlate with distinct gene expression profile and favourable survival in single hormone receptor-positive breast cancer
- Department of Pathology, Medical University of Gdańsk, Gdańsk, Poland
- Department of Oncology, Wrocław Medical University, Wrocław, Poland
- Department of Oncology, Breast Unit, Lower Silesian Oncology Centre, Wroclaw, Poland
- Department of Oncology, Institute of Medical Sciences, University of Opole, Opole, Poland
- Department of Clinical Oncology, Tadeusz Koszarowski Cancer Centre in Opole, Opole, Poland
- Department of Pathology, Chair of Oncology, Medical University of Łódź, Łódź, Poland
- Department of Oncology, Morski Hospital, Gdynia, Poland
- Department of Clinical Oncology, Greater Poland Cancer Centre, Poznań, Poland
- Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska Curie National Research Institute of Oncology, Warsaw, Poland
- Department of Pathology and Neuropathology, Medical University of Gdańsk, Gdańsk, Poland
- Laboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, Gdańsk, Poland
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
Introduction:
This study aimed to evaluate the impact of tumour-infiltrating lymphocytes (TILs) on the expression of immune-related genes and prognosis in single hormone receptor-positive breast cancer.
Material and methods:
Tumour-infiltrating lymphocytes were analysed according to the guidelines of the International TILs Working Group in a cohort of 206 patients with single hormone receptor-positive breast cancer. Of these, 44.7% were classified as ER+/PgR–/HER2–, 18.4% as ER+/PgR–/HER2+, 26.2% as ER–/PgR+/HER2–, and 10.7% as ER–/PgR+/HER2+. Moreover, in 52 samples the analysis of gene expression profiling was performed using nCounter technology.
Results:
Most cases (74.3%) showed at least 1% of stromal TILs, with a median of 4%, mean of 16.3%, and interquartile range of 0–20%. ER–/PgR+ tumours displayed significantly higher TILs density than ER+/PgR– cases (p < 0.001, Wilcoxon test), regardless of HER2 status. The abundance of TILs was positively associated with ER–/PgR+ phenotype, higher Ki-67, and higher grade, but not with age, tumour size, or regional and distant metastases at diagnosis. Additionally, in ER+/PgR– subgroup higher TILs were associated with HER2-positive status. Stromal TILs > 5% were associated with better survival in the whole group, but this effect was less prominent in ER–/PgR+ patients. We identified 50 differentially expressed genes (DEGs) between single hormone receptor-positive breast tumours with high and low TILs, including 39 up-regulated and 11 down-regulated genes in the high TILs group.
Conclusions:
The up-regulated expression of immune-related genes was consistent also among separately analysed single hormone receptor-positive groups (ER+/PgR– and ER–/PgR+).
Keywords
gene expression, tumour infiltrating lymphocytes, prognosis, breast cancer
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