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Published on: September 18, 2020
HER Family Protein Expression in a Greek Population with Gastric Cancer. A Retrospective Hellenic Cooperative
Thomas Makatsoris1, Athanassios C Tsamandas2, Alexios Strimpakos3
1Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece maktom@yahoo.com.
Background:
Gastric cancer is a relatively common malignancy. Recently, the presence of the human epidermal growth factor receptor 2 (HER2) was identified as a molecular target in a proportion of patients who benefited from the addition of appropriate anti-HER2 treatments. Our study explored the clinical and prognostic role of known HER family members, human epidermal growth factor receptor 1 (EGFR or HER1), HER2, HER3 and HER4.
Patients And Methods:
Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 249 gastric cancer patients were studied by immunohistochemistry for protein expression of EGFR, HER2, HER3 and HER4.
Results:
Of the 249 evaluable patients, 32 did not have complete data of treatment details and/or follow-up and were excluded from the survival analyses. Of the 217 patients with complete treatment and follow-up data, 178 were operated and treated for early disease (group 1), while 39 for advanced disease (group 2). The frequency of positive EGFR, HER2, HER3 and HER4 protein expression in all patients was 17.5%, 11.8%, 14.8% and 32.9%, respectively. There were no differences in protein expression of any of the markers between the two groups. There were, however, statistically significant associations between HER4 and all other HER family members, as well as between HER2 and HER3 expression. Of note, EGFR-positive membranous protein expression was significantly associated with the presence of lymphovascular invasion (p=0.027) and HER3 and HER4 negative cytoplasmic protein expression with well/moderately-differentiated tumors (p=0.030 and p=0.014, respectively). None of the HER family members were of prognostic value for OS in univariate analysis.
Conclusion:
The present study confirmed the known protein expression frequencies of HER family members in gastric cancer in a Greek population. Several associations were observed among the HER family members and between clinicopathological characteristics and HER family members. Further research is needed on their exact prognostic role, as well as their therapeutic targeting.
Insights
This study investigated human epidermal growth factor receptor (HER) family members in gastric cancer patients. While HER family members showed associations with each other and some clinicopathological features, they did not demonstrate prognostic value for overall survival.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Gastric cancer is a common malignancy with HER2 identified as a therapeutic target.
- Understanding the role of other HER family members (EGFR, HER3, HER4) is crucial for comprehensive treatment strategies.
Purpose of the Study:
- To explore the clinical and prognostic significance of EGFR, HER2, HER3, and HER4 protein expression in gastric cancer.
- To investigate associations between HER family members and clinicopathological characteristics.
Main Methods:
- Immunohistochemistry was used to assess protein expression of EGFR, HER2, HER3, and HER4 in FFPE tumor samples from 249 gastric cancer patients.
- Survival analyses were performed on patients with complete follow-up data.
Main Results:
- Protein expression frequencies were: EGFR (17.5%), HER2 (11.8%), HER3 (14.8%), and HER4 (32.9%).
- Significant associations were found between HER4 and other HER family members, and between HER2 and HER3 expression.
- EGFR expression correlated with lymphovascular invasion, and HER3/HER4 expression with tumor differentiation. No HER family member showed prognostic value for overall survival.
Conclusions:
- The study confirmed known HER family member expression frequencies in a Greek gastric cancer population.
- Associations among HER family members and with clinicopathological features were identified.
- Further research is warranted to elucidate the prognostic role and therapeutic potential of these targets.
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