Prognostic value of tumor\u2013stroma ratio combined with the immune status of tumors in invasive breast carcinoma

K M H Vangangelt,G W Van Pelt,H Putter,W E Mesker,R A E M Tollenaar,G J Liefers,P J K Kuppen,V T H B M Smit,C C Engels

doi:10.1007/s10549-017-4617-6

K M H Vangangelt, G W Van Pelt + Show 7 more

Open Access

https://doi.org/10.1007/s10549-017-4617-6

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Abstract

PurposeComplex 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.MethodsA 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).ResultsTSR (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.ConclusionsDetermination 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.

Highlights

Survival for patients with invasive breast cancer has increased in the last decade due to new and improved therapeutic options as well as new insights in molecular biology.Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users
In 43% of the cases, no classification of the immune status could be made due to the low quality of tissues or tissue micro-array (TMA)
The loss or damage of TMA cores is a known problem associated with preparation, staining and mounting of TMA slides

Summary

Introduction

Survival for patients with invasive breast cancer has increased in the last decade due to new and improved therapeutic options as well as new insights in molecular biology. Methods to select patients based on the tumor phenotype are important to reduce over- and undertreatment, for example, gene expression profiles that identify subtypes [1, 2] associated with higher risk of metastasis. These techniques result in prognostic and predictive valuable information for specific patient groups, optimization of risk assessment might benefit from further improvement. Suggestions have been made about the influence of tumor stroma on suppression of the immune response [9, 20,21,22,23] In this present study, the prognostic value of the interplay between tumor–stroma ratio (TSR) and the immune status of tumors in breast cancer patients was evaluated. We hypothesize that stroma-high tumors in combination with a low immune status behave more aggressively resulting in a high risk of disease progression

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Conclusion

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