HER2 testing in paired biopsy and excision specimens of gastric cancer: the reliability of the scoring system and the clinicopathological factors relevant to discordance

Abstract

Background Inclusion of trastuzumab in chemotherapy regimens is advantageous for patients with advanced or metastatic gastric cancer who overexpress HER2. Therefore, accurate assessment of HER2 status in tumor tissue is critical when weighing treatment options. Methods We examined HER2 expression in 180 paired endoscopic biopsy and surgical excision specimens of gastric cancers via immunohistochemistry (IHC). Equivocal IHC results (IHC 2?) were resolved by HER2 fluorescence in situ hybridization (FISH). The relationships of several clinical and pathological features with discordant HER2 results in paired specimens were determined. Results Fourteen biopsy specimens and surgical specimens (7.8 %) were HER2-positive. Discordant HER2 IHC scores were observed in 90 paired specimens (50 %) and 8 paired specimens (4.4 %) had discordant results. The kappa coefficients for an HER2 diagnostic algorithm were 0.264, 0.339, and 0.690 for IHC scores, IHC categories, and final results, respectively (p \ 0.001). Discordant HER2 results were significantly associated with discordant tumor differentiation in the paired biopsy and excision specimens (p = 0.01). Intratumoral heterogeneity did not predict HER2 discordance. There was no association between HER2 discordance and the number of biopsy tissue fragments (p = 0.764). Conclusions Hofmann's HER2 scoring system is a fairly reliable tool for evaluating HER2 status in biopsy and excision specimens. Discordant HER2 results in paired specimens were observed in a small percentage of gastric cancers. Testing all available specimens should be considered in order to eliminate discrepancies, especially when discordant tumor differentiation is observed.

HER2-Neu Gene Testing in Gastric Cancer by Immunohistochemistry in Tunisian Patient’ Samples

“…But Saito et al [10], in a series of 224 patients, they found 21% of tissues were HER2-positive. Furthermore, Huang et al determined only a proportion of 7.8% of HER2-positive in fourteen biopsy and surgical specimens [8]. However, in the study of Rajagopal et al, in 60 cases, positive HER2 expression was observed only in In their study, they demonstrated a significant difference in the overexpression of HER2/neu in gastric tumors.…”

“…The HER2 protein is a member of the epidermal growth factor receptor family and is coded by HER2/neu gene located on the long arm of chromosome 17 [8]. The product is a 185 kD transmembrane glycoprotein [9].…”

“…The product is a 185 kD transmembrane glycoprotein [9]. It is a transmembrane tyrosine kinase receptor [3], involved in tumor cell proliferation, apoptosis, adhesion, migration, and differentiation [8].…”

Poor efficacy response to trastuzumab therapy in advanced gastric cancer with homogeneous HER2 positive and non-intestinal type

“…In this study, HER2 status of 36 patients was evaluated in biopsy specimens which have been shown to be highly consistent with surgical specimens [32–34]. To predict HER2 precisely, 4 tumor-containing fragments were recommended [35].…”

Tumor containing fragment number influences immunohistochemistry positive rate of HER2 in biopsy specimens of gastric cancer

“…Assessment of HER2 status in GC is challenging because of the protein’s affinity for being heterogeneously expressed [4–6]. For endoscopic biopsy specimens, it is a far more serious issue in that biopsy specimens are less manageable than resected specimens in HER2 assessment due to unpredictable tumor tissue amount.…”