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. 2018 Apr;168(3):601-612.
doi: 10.1007/s10549-017-4617-6. Epub 2017 Dec 22.

Prognostic value of tumor-stroma ratio combined with the immune status of tumors in invasive breast carcinoma

K M H Vangangelt  1 , G W van Pelt  1 , C C Engels  1 , H Putter  2 , G J Liefers  1 , V T H B M Smit  3 , R A E M Tollenaar  1 , P J K Kuppen  1 , W E Mesker  4
Affiliations

Prognostic value of tumor-stroma ratio combined with the immune status of tumors in invasive breast carcinoma

K M H Vangangelt et al. Breast Cancer Res Treat. 2018 Apr.

Abstract

Purpose: Complex interactions occur between cancer cells and cells in the tumor microenvironment. In this study, the prognostic value of the interplay between tumor-stroma ratio (TSR) and the immune status of tumors in breast cancer patients was evaluated.

Methods: A cohort of 574 breast cancer patients was analyzed. The percentage of tumor stroma was visually estimated on Hematoxylin and Eosin (H&E) stained histological tumor tissue sections. Immunohistochemical staining was performed for classical human leukocyte antigen (HLA) class I, HLA-E, HLA-G, markers for regulatory T (Treg) cells, natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs).

Results: TSR (P < .001) and immune status of tumors (P < .001) were both statistically significant for recurrence free period (RFP) and both independent prognosticators (P < .001) in which tumors with a high stromal content behave more aggressively as well as tumors with a low immune status. Ten years RFP for patients with a stroma-low tumor and high immune status profile was 87% compared to 17% of patients with a stroma-high tumor combined with low immune status profile (P < .001). Classical HLA class I is the most prominent immune marker in the immune status profiles.

Conclusions: Determination of TSR is a simple, fast and cheap method. The effect on RFP of TSR when combined with immune status of tumors or expression of classical HLA class I is even stronger. Both are promising for further prediction and achievement of tailored treatment for breast cancer patients.

Keywords: Breast cancer; HLA; Immune cells; Prognosis; Tumor–stroma ratio.

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Conflict of interest statement

Conflict of interest

The authors declare no potential conflicts of interest. This study has not been presented elsewhere. No Disclaimers.

Ethical standards

The experiments which were performed comply with the current laws of the country.

Figures

Fig. 1
Fig. 1
Evaluation of immune status and classification. HLA human leukocyte antigen, CTL cytotoxic T-lymphocytes, Treg regulatory T cells, NK natural killer
Fig. 2
Fig. 2
Flowchart of subject inclusion. * For categorizing in one of the three immune status categories not all six groups need to be known. FFPE formalin-fixed paraffin-embedded, NK natural killer, CTL cytotoxic T-lymphocyte, Treg regulatory T, TSR tumor–stroma ratio
Fig. 3
Fig. 3
Kaplan–Meier analysis for RFP of TSR, immune status profiles and classical HLA class I. a RFP for stroma low and high tumors, b RFP for three IS profiles, c RFP for TSR combined with IS profiles, d RFP for TSR combined with classical HLA class I. IS immune status, RFP recurrence free period, TSR tumor–stroma ratio
See this image and copyright information in PMC

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