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FGFR1 and HER1 or HER2 co-amplification in breast cancer indicate poor prognosis.

ABSTRACT: Human epidermal growth factor receptor 1 or 2 (HER1/2), and fibroblast growth factor receptor 1 (FGFR1) signaling serve critical roles in the progression of breast cancer; however, cross-talk between HER1/2 and FGFR1 signaling has not been extensively studied. In the present study, the copy number variation status of FGFR1 and HER1/2, and the clinical implications and prognostic relevance of this, were evaluated in invasive ductal breast cancer (IDC) tissue samples. Quantitative polymerase chain reaction and fluorescence in situ hybridization were used to assess gene copy number variation in IDC samples, and the clinical characteristics and survival curves of patients with IDC were analyzed. The amplification of FGFR1 was identified in 16.0% of the samples (12 of 75), of HER1 in 26.7% (20 of 75), of HER2 in 37.3% (28 of 75), and of FGFR1 and HER1/2 simultaneously in 8.0% (6 of 75). FGFR1 and HER1/2 co-amplification were significantly correlated with distant metastasis (P=0.035), recurrence (P=0.026) and decreased disease-free survival time (P=0.042). This was the case for patients undergoing endocrine therapy (P=0.002) and chemotherapy (P=0.044). Taken together, the results indicate that patients with FGFR1 and HER1/2 co-amplification may exhibit a less favorable prognosis compared with patients with either FGFR1, HER1/2 amplification or without amplification.

SUBMITTER: Chen S

PROVIDER: S-EPMC5950032 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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FGFR1 and HER1 or HER2 co-amplification in breast cancer indicate poor prognosis.

Chen Shinan S Qiu Yan Y Guo Peng P Pu Tianjie T Feng Ye Y Bu Hong H

Oncology letters 20180404 6

Human epidermal growth factor receptor 1 or 2 (HER1/2), and fibroblast growth factor receptor 1 (FGFR1) signaling serve critical roles in the progression of breast cancer; however, cross-talk between HER1/2 and FGFR1 signaling has not been extensively studied. In the present study, the copy number variation status of FGFR1 and HER1/2, and the clinical implications and prognostic relevance of this, were evaluated in invasive ductal breast cancer (IDC) tissue samples. Quantita ...[more]

PMID: 29805554

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Project description:ErbB signaling serves essential roles in invasive ductal carcinoma (IDC). The aim of the present study was to assess gene amplification in ErbB family members in IDC with clinical implications. Quantitative polymerase chain reaction and fluorescence in situ hybridization were performed on formalin-fixed paraffin-embedded tumor samples for gene amplification detection. The clinical and histopathological characteristics, as well as the prognostic significance, were analyzed. Among the 119 IDC patients evaluated, epidermal growth factor receptor [EGFR; also known as human epidermal growth factor receptor (HER)1], HER2, HER3 and HER4 gene amplification was observed in 30 (25.2%), 44 (36.9%), 0 (0.0%) and 1 (0.8%) patients, respectively. EGFR amplification was associated with estrogen receptor status (P=0.028) and higher possibilities of recurrence (P=0.015) and distant metastasis (following initial surgery) (P=0.011). In survival analysis, EGFR amplification was also associated with disease-free survival (DFS) (P=0.001) and overall survival (OS) (P=0.003). HER2 amplification was associated with larger tumor size (P=0.006), later clinical stage (P=0.003) and distant metastasis (following initial surgery) (P=0.006). In survival analysis, HER2 amplification was also associated with DFS (P=0.011). Notably, the present study identified a group of patients in whom EGFR and HER2 were co-amplified. This group of patients appeared to have a higher possibility of metastasis (when diagnosed) (P=0.014) and distant metastasis (following initial surgery) (P<0.001). In survival analysis, these patients were noticed to be associated with DFS (P<0.001) and OS (P=0.002). With respect to treatment regimen, this was also true for the DFS association with chemotherapy (P<0.001), radiotherapy (P<0.001) and hormonal therapy (P=0.001). The present results suggest that EGFR and HER2 amplification favor distant metastasis following initial surgery and are significantly associated with poor clinical outcome in breast cancer patients.

Project description:Breast cancer (BC) is one of the most common types of malignancies in women and greatly threatens female health. KRT17 is a member of the keratin (KRT) protein family that is abundant in the outer layer of the skin, where it protects epithelial cells from damage. Although KRT17 has been studied in many types of cancer, the expression of KRT17 in specific subtypes of BC remains to be determined. In our study, we explored the expression and prognostic implications of KRT17 in BC patients using mRNA transcriptome data and clinical BC data from The Cancer Genome Atlas (TCGA). Receiver operating characteristic (ROC) curves and the chi-square test were used to assess the diagnostic value of KRT17 expression. Quantitative real-time PCR (qRT-PCR) analysis of BC cells and tissues and immunohistochemistry (IHC) analysis of clinical tissues were used for external validation. Furthermore, the relationship between KRT17 and immune function was studied by using the CIBERSORT algorithm to predict the proportions of tumor-infiltrating immune cells (TIICs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the potential mechanisms by which KRT17 expression influences patient survival. We found that KRT17 expression was significantly lower in BC tissues than in normal tissues, especially in the luminal-A, luminal-B and human epidermal growth factor receptor-2 (HER2)+ subtypes of BC. ROC analysis revealed that KRT17 expression had moderate diagnostic value. Interestingly, decreased expression of KRT17 was significantly correlated with poor prognosis in BC patients, especially in HER2high and ERhigh patients. This trend was also verified by tissue microarray (TMA) analysis. KRT17 was found to be involved in some antitumor immune pathways, especially the IL-17 signaling pathway, and associated with multiple immune cells, such as natural killer (NK) and CD4+ T cells. In conclusion, high expression of KRT17 predicted favorable prognosis in BC patients with higher HER2 expression. This result may indicate that KRT17 plays a different role depending on the level of HER2 expression and could serve as a promising and sensitive biomarker for the diagnosis and prognostication of HER2high BC.

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FGFR1 and HER1 or HER2 co-amplification in breast cancer indicate poor prognosis.

Publications

<i>FGFR1</i> and <i>HER1</i> or <i>HER2</i> co-amplification in breast cancer indicate poor prognosis.

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