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Human epidermal growth factor receptor 2 (HER-2) status evaluation in advanced gastric cancer using immunohistochemistry versus silver in situ hybridization

Nuray Kepil, Sebnem Batur, Ceyda Sonmez Wetherilt, Sibel Erdamar Cetin


Accurate identification of human epidermal growth factor receptor 2 (HER-2) status in advanced gastric cancer patients is of utmost importance in terms of treatment planning. This study aimed to examine the HER-2 status in advanced gastric cancer patients using both immunohistochemistry (IHC) and silver in situ hybridization (SISH) techniques and to investigate concordance and diagnostic accuracy. In addition, associations between clinical parameters and HER 2 status were examined. A total of 313 patients diagnosed with locally advanced (Stage III: T3-4, N+) recurrent or metastatic adenocarcinoma of the stomach or esophagogastric junction, between 2009 and 2015, were included. HER-2 status was examined using both IHC and SISH techniques and the findings were compared. Overall SISH-confirmed HER-2 positivity rate was 22%. Multivariate analysis identified only well-differentiated tumor as a significant predictor of HER-2 positivity (OR: 2.9, 95% CI: 1.4-5.9, p = 0.003). When IHC 2+ and 3+ were considered positive for HER-2 status, sensitivity, specificity, and concordance rate (κ) was 95.7%, 93.8%, and 0.84, respectively. Corresponding figures when only IHC 3+ cases were considered positive were lower: 50%, 100%, and 0.61, respectively. The present method used for the identification of HER-2 positive gastric cancer patients provides satisfactory results. However, better categorization of IHC 2+ cases has the potential to improve the diagnostic accuracy, which is particularly important when more sophisticated methods are not readily available.


Human epidermal growth factor receptor 2; gastric cancer; immunohistochemistry; silver in situ hybridization

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