Tumor Infiltrating Lymphocytes Affect the Outcome of Patients with Operable Triple-Negative Breast Cancer in Combination with Mutated Amino Acid Classes.
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.
Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.|Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.
Vassiliki
V
Kotoula
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.
Sotiris
S
Lakis
Molecular Diagnostics Laboratory, INRASTES, NCSR 'Demokritos', Athens, Greece.|DIANA-Lab, Department of Computer and Communication Engineering, University of Thessaly, Volos, Greece.
Ioannis S
IS
Vlachos
Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.|The University of New South Wales, New South Wales, Australia.
Eleni
E
Giannoulatou
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Flora
F
Zagouri
Department of Biostatistics, Health Data Specialists Ltd, Athens, Greece.
Zoi
Z
Alexopoulou
First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Helen
H
Gogas
Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece.
Dimitrios
D
Pectasides
Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece.
Gerasimos
G
Aravantinos
Department of Pathology, Papageorgiou Hospital, Thessaloniki, Greece.
Ioannis
I
Efstratiou
Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece.
George
G
Pentheroudakis
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.
Kyriaki
K
Papadopoulou
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.
Kyriakos
K
Chatzopoulos
Oncology Unit, Hippokration Hospital, Athens, Greece.
Pavlos
P
Papakostas
Department of Pathology, Alexandra Hospital, Athens, Greece.
Maria
M
Sotiropoulou
Department of Histopathology, Agii Anagriri Cancer Hospital, Athens, Greece.
Irene
I
Nicolaou
Third Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
Evangelia
E
Razis
Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece.
Amanda
A
Psyrri
Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
Paris
P
Kosmidis
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Christos
C
Papadimitriou
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.|Aristotle University of Thessaloniki, Thessaloniki, Greece.
George
G
Fountzilas
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