HER2 expression and its clinicopathological features in resectable gastric cancer

Kataoka, Yoshiki; Okabe, Hiroshi; Yoshizawa, Akihiko; Minamiguchi, Sachiko; Yoshimura, Kenichi; Haga, Hironori; Sakai, Yoshiharu

doi:10.1007/s10120-012-0150-9

Cited by 77 publications

(70 citation statements)

References 35 publications

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“…Regarding anatomical location similar finding have been reported, with no difference between proximal and distal tumor, as we have found in our study (3,9,10,14,18,21) . Most studies conducted in Asia have also reported reactivity rates of 11.7% to 15.74%, similar to our findings, as well as the predominance of HER2 expression in the intestinal subtype (11,16,17,22) . Only one study from Japan showed different prevalence of HER2 expression regarding to anatomical distribution.…”

Section: Discussionsupporting

confidence: 91%

Immunohistochemical Expression of Her2 in Adenocarcinoma of the Stomach

Carli

Rocha

Antunes

et al. 2015

Arq. Gastroenterol.

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-Background -Worldwide, gastric cancer is the fourth cancer in incidence and the second most common cause of cancer death. Gastric cancer is asymptomatic in the early stages and very often diagnosed at advanced stages, determining a dismal prognosis. Expression of the HER2 gene has been identified in about 20% of gastric cancer cases, and its hyper-expression is associated with poor prognosis. Objective -To investigate HER2 immunohistochemical expression in gastric adenocarcinoma and its relationship to the histological type and anatomic location. Methods -A cross-sectional retrospective study analyzed the immunohistochemical expression of HER2 in a sample of 48 specimens of gastric cancer. Immunohistochemical analysis were performed using avidin-biotin-peroxidase method with C-erb B2 (clone EP1045Y), as a primary antibody (Biocare Medical, USA). Standardized gastric adenocarcinoma's HER2 expression criteria has been used in the analysis of samples. Results -There were seven cases with reactivity for HER2. Five were of intestinal-type while two cases were of mixed-type in which the expression occurred in the intestinal component. It was identified a significant association of HER2 expression in the intestinal subtype of gastric adenocarcinoma (P=0.003).Regarding the anatomical site, HER2 was positive in only one (16.6%) of the six proximal cases and six (14.28%) of the 42 distal cases (P=0.88). Conclusion -HER2 immunoexpression was identified in 14.6% of the samples, and the expression was significantly associated to Lauren's intestinal subtype. HEADINGS -Immunohistochemistry. Stomach neoplasms. erbB-2 genes.

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Section: Discussionsupporting

confidence: 91%

Immunohistochemical Expression of Her2 in Adenocarcinoma of the Stomach

Carli

Rocha

Antunes

et al. 2015

Arq. Gastroenterol.

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“…Regarding HER2 and EGFR, our results were similar to those of previous reports with regard to the clinicopathological features and prognosis of each RTK-overexpressing tumor [26,[36][37][38][39][40][41]. However, contrary to previous reports, MET-overexpressing GACs tended to be associated with a rather favorable outcome in our study [25,42,43].…”

Section: Discussionsupporting

confidence: 89%

“…Previous reports also have shown that only a portion of protein expression cases exhibit gene amplification [24][25][26], so gastric cancers with RTK protein overexpression might be derived not only from RTK gene amplification, but also via other mechanisms. Regarding treatment, since gastric cancers with strong or moderate overexpression of HER2 protein plus gene amplification are associated with the efficacy of trastuzumab, gene amplification does not necessarily surpass protein expression with regard to predicting the effect of targeted therapy with antibodies [5].…”

Section: Discussionmentioning

confidence: 96%

Expression profiles of HER2, EGFR, MET and FGFR2 in a large cohort of patients with gastric adenocarcinoma

et al. 2014

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Background Some tyrosine kinase receptors (RTKs) play critical roles in gastric cancer progression. Not only trastuzumab, but also several other agents targeting RTKs are being investigated for gastric cancer therapy. However, the simultaneous expression of multiple RTKs, which may interfere with the effectiveness of therapeutic agents, has not been evaluated in a large cohort with gastric adenocarcinoma (GAC). Methods We performed a tissue microarray analysis in 950 patients with GAC who underwent a gastrectomy without preoperative chemotherapy. The protein expressions of HER2, EGFR, MET and FGFR2 were evaluated using immunohistochemistry, and the gene amplifications of HER2, EGFR and MET were examined using dual-color in situ hybridization.Results The frequency of overexpression was 11.8 % for HER2, 23.5 % for EGFR, 24.9 % for MET and 31.1 % for FGFR2. Whereas strong staining for each of the RTKs was heterogeneous, tumors with homogeneously strong staining areas often exhibited gene amplification. Strong EGFR expression was significantly associated with a poor outcome, but no prognostic correlations were observed in other RTKs. The overexpression of single and multiple RTKs was observed in 40.4 and 22.7 % of the cases, respectively. HER2, EGFR, MET and FGFR2 predominance was observed in 10.1, 13.9, 16.1 and 22.9 % of the GACs, respectively. Conclusions Approximately two-thirds of patients with GAC exhibited the expression of at least one RTK and would be candidates for targeted therapies. Moreover, one-third of at least one RTK overexspressing cases showed multiple RTKs expression. Our results may be useful for selecting the most suitable patients for each targeted therapy.

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“…Detailed HER2 expression in the primary tumor with various stages and the concordance of HER2 expression between the primary tumor and general metastases have been reported in breast and gastric cancers [13,14], but no detailed EGFR and HER2 expression focused on liver and peritoneal metastases has been reported in gastric cancers [15,16]. In the present study, we investigated the EGFR and HER2 expression in the primary tumor and corresponding liver and peritoneal metastases, and in partly lymph node metastases, in patients with advanced gastric cancer and demonstrated their preferential HER2 and EGFR expression in the liver metastases and peritoneal metastases, respectively.…”

Section: Introductionmentioning

confidence: 99%

Preferential HER2 expression in liver metastases and EGFR expression in peritoneal metastases in patients with advanced gastric cancer

et al. 2014

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Background Despite recent clinical trials, the sensitivity and resistance of metastatic gastric cancer to anti-HER2 and anti-EGFR therapy are still unclear. Materials and methods To clarify the HER2 and EGFR expression status in the metastatic sites, we immunohistochemically compared HER2 and EGFR expression between primary and metastatic tumors from 52 gastric cancer patients with liver metastases and 85 patients with peritoneal metastases. Results The HER2 positivity rate of primary and metastatic tumors in patients with liver metastases, especially with intestinal-type histology (70.6 and 80.0 %, respectively), was significantly higher than in primary and metastatic tumors (22.4 and 16.4 %, respectively) in patients with peritoneal metastases. HER2 positivity of the primary tumor and liver metastases showed good concordance (87.5 %) in patients with liver metastases. In contrast, the EGFR positivity rate of metastatic tumors (70.1 %) in patients with peritoneal metastases was significantly higher than that of metastatic tumors (37.5 %) in patients with liver metastases. HER2 and EGFR expression tended to be mutually exclusive, and HER2/EGFR double-positive cases were rare in patients with liver or peritoneal metastases. In four such patients with HER2/EGFR double-positive primary tumors, the HER2-and EGFR-positive areas were separate, and corresponding liver metastasis was only positive for HER2 and peritoneal metastasis only positive for EGFR. Conclusion These results indicate that HER2 and EGFR are preferentially expressed in the liver and peritoneal metastases, respectively, which would be potential targets for anti-HER2 and anti-EGFR molecular therapy in metastatic gastric cancer patients.

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HER2 expression and its clinicopathological features in resectable gastric cancer

Cited by 77 publications

References 35 publications

Immunohistochemical Expression of Her2 in Adenocarcinoma of the Stomach

Immunohistochemical Expression of Her2 in Adenocarcinoma of the Stomach

Expression profiles of HER2, EGFR, MET and FGFR2 in a large cohort of patients with gastric adenocarcinoma

Preferential HER2 expression in liver metastases and EGFR expression in peritoneal metastases in patients with advanced gastric cancer

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