Kotoula, Vassiliki and Lakis, Sotiris and Vlachos, Ioannis S and Giannoulatou, Eleni and Zagouri, Flora and Alexopoulou, Zoi and Gogas, Helen and Pectasides, Dimitrios and Aravantinos, Gerasimos and Efstratiou, Ioannis and Pentheroudakis, George and Papadopoulou, Kyriaki and Chatzopoulos, Kyriakos and Papakostas, Pavlos and Sotiropoulou, Maria and Nicolaou, Irene and Razis, Evangelia and Psyrri, Amanda and Kosmidis, Paris and Papadimitriou, Christos and Fountzilas, George (2016) Tumor Infiltrating Lymphocytes Affect the Outcome of Patients with Operable Triple-Negative Breast Cancer in Combination with Mutated Amino Acid Classes. PloS One, 11 (9). pp. e0163138. ISSN 1932-6203 (Gold OA)
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Abstract
BACKGROUND
Stromal tumor infiltrating lymphocytes (TILs) density is an outcome predictor in triple-negative breast cancer (TNBC). Herein we asked whether TILs are related to coding mutation load and to the chemical class of the resulting mutated amino acids, i.e., charged, polar, and hydrophobic mutations.
METHODS
We examined paraffin tumors from TNBC patients who had been treated with adjuvant chemotherapy mostly within clinical trials (training cohort, N = 133; validation, N = 190) for phenotype concordance; TILs density; mutation load and types.
RESULTS
Concordance of TNBC phenotypes was 42.1% upon local / central, and 72% upon central / central pathology assessment. TILs were not associated with mutation load, type and class of mutated amino acids. Polar and charged mutation patterns differed between TP53 and PIK3CA (p<0.001). Hydrophobic mutations predicted for early relapse in patients with high nodal burden and <50% TILs tumors (training: HR 3.03, 95%CI 1.11-8.29, p = 0.031; validation: HR 2.90, 95%CI 0.97-8.70, p = 0.057), especially if compared to patients with >50% TILs tumors (training p = 0.003; validation p = 0.015).
CONCLUSIONS
TILs density is unrelated to mutation load in TNBC, which may be regarded as an unstable phenotype. If further validated, hydrophobic mutations along with TILs density may help identifying TNBC patients in higher risk for relapse.
| Item Type: | Article |
|---|---|
| Additional Information: | This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 04 Oct 2016 00:12 |
| Last Modified: | 04 Oct 2016 00:12 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/493 |
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