Clinicopathological Features, Tumor Mutational Burden, and Tumour-Infiltrating Lymphocyte Interplay in ERBB2-Mutated Breast Cancer: In Silico Analysis.
Pathol Oncol Res
; 27: 633243, 2021.
Article
in En
| MEDLINE
| ID: mdl-34257600
ABSTRACT
Recent evidence suggests that somatic mutations in ERBB2 activate ERBB2 signaling. These mutations occur at a frequency of approximately 3% in breast cancer (BC). ERBB2 mutations indicate poor prognosis as they are associated with recurrence and metastasis. This study aimed to evaluate the clinicopathological features, immune infiltration levels, tumor mutational burden (TMB), and tumor-infiltrating lymphocytes (TILs) in ERBB2-mutated breast cancer (ERBB2-mutated BC) using a bioinformatic approach and publicly available datasets (i.e., TCGA-BRCA and TIMER2.0). ERBB2-mutated BCs were associated with a high histological grade. ERBB2-mutated BCs comprised invasive breast carcinoma of no special type (21/35, 60%), classic invasive lobular carcinoma (12/35, 34.3%), and pleomorphic invasive lobular carcinoma (2/35, 5.7%). A Kaplan-Meier survival curve demonstrated that ERBB2-mutated BC was associated with a significantly worse prognosis compared to ERBB2 non-mutated BC (p < 0.01). Furthermore, 40% (14/35) of the patients with ERBB2-mutated BC harbored CDH1 mutations. Mutations at L755 and V777 accounted for 30.5% of these mutations in ERBB2-mutated BC, suggesting that these sites are mutational hot spots in BC, particularly in invasive lobular carcinoma. Of the ERBB2-mutated BCs, 8.6% were classified as TIL-high, whereas 77.1% were TILs-low; TMB significantly correlated with TILs (p < 0.05). CD8+ T cell infiltration levels were significantly higher in ERBB2 non-mutated BC. Among ERBB2-mutated BCs, 22.9% were classified as TMB-high, which was significantly higher than the rate in the ERBB2 non-mutated BC (p < 0.01). These findings provide evidence for a link between ERBB2 mutations and high TMB in BC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Biomarkers, Tumor
/
Lymphocytes, Tumor-Infiltrating
/
Carcinoma, Lobular
/
Receptor, ErbB-2
/
Mutation
/
Neoplasm Recurrence, Local
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Pathol Oncol Res
Journal subject:
NEOPLASIAS
/
PATOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
Japan