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Human epidermal growth factor receptor-2/neu expression in gallbladder cancer is significantly associated with
Sashibhusan Dash1,2, Prajna Anirvan3, Sagarika Samantaray1
1Department of Pathology, Acharya Harihar Postgraduate Institute of Cancer, Cuttack 753 007, India.
Background:
Anti-human epidermal growth factor receptor-2 (Her-2/neu) target therapy has substantially improved the disease outcome of patients with breast and gastric/gastroesophageal cancers characterized by Her-2/neu overexpression and/or amplification. Consequently, evaluating Her-2/neu expression in other cancers to predict response to Her-2/neu targeting agents emerges as a crucial approach. We aimed at investigating the positivity rate of this receptor in gallbladder cancer (GBC) and assess the relationship between Her-2/neu status, clinicopathological parameters and survival to identify patients who would benefit most from anti-Her-2/neu-targeted therapy. The Her-2/neu expression was correlated with clinicopathological parameters and survival of GBC cases.
Methods:
Total 235 surgically resected and histopathologically proven primary GBC cases were collected over a five-year period from January 1, 2017, to December 31, 2020. Her-2/neu expression in these cases was analyzed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
Results:
Employing testing algorithms (IHC scoring based on gastric cancer criteria, followed by FISH in equivocal cases), Her-2/neu positivity was identified in 43 (18.29%) GBC cases and was significantly associated with grade-I tumors, tumor stage > T2, perineural invasion, surgical margin positivity and advanced Tumor-Node-Metastasis (TNM) stage. The mean survival time for Her-2/neu-positive cases was 14 months (SE, 1.1; 95% CI, 11.7-16.06), while it was 20 months (SE, 0.69; 95%CI, 18.1-20.9) for Her-2-negative cases (p < 0.001).
Conclusion:
Her-2/neu is expressed in about one-fifth of GBC patients and is significantly associated with tumor behavior and patient survival. Utilizing novel targeted agents may hold the key to improving the prognosis of these patients.
Insights
Human epidermal growth factor receptor-2 (Her-2/neu) is expressed in about one-fifth of gallbladder cancer patients, correlating with poorer survival. This suggests potential benefit from Her-2/neu targeted therapies for this patient group.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Anti-human epidermal growth factor receptor-2 (Her-2/neu) targeted therapy has improved outcomes in breast and gastric cancers.
- Evaluating Her-2/neu expression in other cancers is crucial for identifying potential responders to Her-2/neu targeting agents.
- Gallbladder cancer (GBC) is a malignancy where Her-2/neu expression and its therapeutic implications are not well-established.
Purpose of the Study:
- To investigate the positivity rate of Her-2/neu expression in gallbladder cancer (GBC).
- To assess the relationship between Her-2/neu status and clinicopathological parameters in GBC.
- To determine the correlation between Her-2/neu status and patient survival in GBC to identify potential candidates for targeted therapy.
Main Methods:
- A cohort of 235 surgically resected primary GBC cases was analyzed.
- Her-2/neu expression was evaluated using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for equivocal cases.
- Data were collected over a five-year period (January 1, 2017, to December 31, 2020).
Main Results:
- Her-2/neu positivity was identified in 18.29% (43 out of 235) of GBC cases.
- Her-2/neu positivity was significantly associated with grade-I tumors, tumor stage > T2, perineural invasion, positive surgical margins, and advanced TNM stage.
- Mean survival time was significantly shorter for Her-2/neu-positive cases (14 months) compared to Her-2-negative cases (20 months) (p < 0.001).
Conclusions:
- Her-2/neu is expressed in a notable proportion of GBC patients, indicating its relevance in this cancer type.
- Her-2/neu expression in GBC is significantly associated with aggressive tumor behavior and reduced patient survival.
- Targeted anti-Her-2/neu agents may offer a promising therapeutic strategy to improve the prognosis for a subset of GBC patients.
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