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Human epidermal growth factor receptor-2/neu expression in gallbladder cancer is significantly associated with clinicopathological parameters and survival

Indian J Gastroenterol. 2025 Feb 3. doi: 10.1007/s12664-024-01723-x. Online ahead of print.

ABSTRACT

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, and 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 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).

CONCLUSIONS: 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.

PMID:39899204 | DOI:10.1007/s12664-024-01723-x

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