Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer

Yano, Tomonori; Doi, Toshihiko; Ohtsu, Atsushi; Boku, Narikazu; Hashizume, Kaoru; Nakanishi, Mamoru; Ochiai, Atsushi

doi:10.3892/or.15.1.65

Cited by 158 publications

(158 citation statements)

References 22 publications

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“…between duplicate TMAs constructed from the same tissue section in a patient were 74.5 and 91.8 %, respectively. Although this was in good agreement with the previously reported results of analysis of biopsy specimens from 261 patients with invasive intestinal-type gastric cancers [25], further investigations are still required to elucidate the reliability of HER2 scoring in TMA samples in gastric cancer.…”

Section: Discussionsupporting

confidence: 81%

Evaluation of HER2-based biology in 1,006 cases of gastric cancer in a Japanese population

et al. 2013

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Background The ToGA trial demonstrated the beneficial effect of trastuzumab in gastric cancer patients with human epidermal growth factor receptor 2 (HER2)-overexpressing tumors. Therefore, evaluation of the relationship between HER2 expression and gastric cancer biology using a validated system has become an even more important task. Herein, we verified the correlation between HER2 overexpression in the tumor and the clinical course of gastric cancer patients. Methods A total of 1,006 consecutive patients with gastric cancer who underwent surgery at the National Cancer Center Hospital East between January 2003 and July 2007 were examined using the tissue microarrays approach. HER2 expression was determined based on an immunohistochemistry score of 3?, or an immunohistochemistry score of 2? plus HER2 gene amplification as detected by double-color fluorescent in situ hybridization. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Then, in 948 patients who had undergone curative resection, HER2 status was compared with the survival.Results HER2 overexpression was detected in 118 (11.7 %) patients. HER2 overexpression was correlated with age, gender, grade of differentiation, expanding growth pattern, and nodal status. In the survival analysis, HER2 overexpression was not found to be correlated with either disease-specific survival or recurrence-free survival. Conclusions HER2 overexpression in the tumor was not identified as a significant prognostic factor in patients with operable gastric cancer. The HER2-targeted therapy may be beneficial in a proportion of cases.

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Section: Discussionsupporting

confidence: 81%

Evaluation of HER2-based biology in 1,006 cases of gastric cancer in a Japanese population

et al. 2013

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“…It has been reported to be overexpressed in 20% of breast and 22% of gastric cancers, although different studies have reported varying results (Bang et al, 2010;Arteaga et al, 2011). In a study investigating 200 patients, HER2 overexpression was reported in 23% of patients, while another study that analyzed 248 patients showed overexpression of HER2 mRNA and/or proteins and amplification of genes in 22.6% of patients (Yano et al, 2006;. In routine clinical practice, HER2 status is usually assessed by IHC or FISH/CISH/SISH techniques in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Is Her-2 Status in the Primary Tumor Correlated with Matched Lymph Node Metastases in Patients with Gastric Cancer Undergoing Curative Gastrectomy?

Selçukbiricik

Erdamar²,

Büyükünal³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: HER2 expression in the primary tumor and its lymph node metastases vary in gastric cancer, reflecting intratumoral heterogeneity. This finding also suggests that proliferation of a different clone in metastatic nodes is possible. In the current study, we aimed to determine the cause of discordance in HER-2 expression in the primary tumor and lymph node metastases for patients with gastric cancer. Materials and Methods: Eighty-one patients with gastric cancer who had undergone radical gastrectomy and were found to have lymph node metastasis upon pathological examination were included. Histopathological samples were obtained from biopsies obtained during patient gastrectomies and lymph node dissection. HER2 status was evaluated by both immunohistochemistry (IHC) and silver in situ hybridization (SISH). Results: Sixty-four (79%) patients were SISH (-), while 17 (21%) were SISH (+) in the primary tumor. However, in metastatic lymph nodes, HER2 status was SISH positive in 5 (28.3%) of the 64 SISH (-) primary tumor specimens. One of the 17 SISH (+) primary tumors was SISH (-) in the metastatic lymph nodes. Thus, SISH results for HER2 in both primary tumors and lymph node metastases were comparable, showing a concordance of 92.5%. In total, six patients demonstrated discordance between the primary tumor and lymph node metastases. The prevalence of HER2 discordance was significantly higher for patients in the pN2 and N3 stages (p=0.007). Although discordant patients had worse survival rates than concordant patients, the differences were not significant (p>0.05).Conclusions: Our study indicates that the frequency of concordance in HER2 status, as determined by IHC or SISH, is high in primary tumors and their corresponding lymph node metastases for patients with gastric cancer. If there is a discrepancy in HER2 status, its evaluation by both IHC and SISH may be useful for detecting patients who would benefit from trastuzumab, and it would therefore help guide decision-making processes in administering treatment.

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“…These findings clearly show that CD90 potentially has a value as a target for immunotherapy. ERBB2 amplification is found in 20-30% of gastric carcinomas and is reported to be significantly associated with shorter survival of cancer patients (Tanner et al, 2005;Yano et al, 2006;Marx et al, 2009). How ERBB2 signaling affects tumor growth, invasion and metastasis is still not clear.…”

Section: Discussionmentioning

confidence: 99%

“…The ERBB2 (HER2) gene is amplified in approximately 20-30% of human breast and gastric cancers, in which it is associated with aggressive disease and early development of metastasis (Slamon et al, 1989;Tanner et al, 2005;Yano et al, 2006). A significant correlation between ERBB2 overexpression and expression of the stem cell marker ALDH1 has been found in a series of 491 breast cancer patients (Ginestier et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

et al. 2011

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Identification and characterization of cancer stem cells (CSCs) in gastric cancer are difficult owing to the lack of specific markers and consensus methods. In this study, we show that cells with the CD90 surface marker in gastric tumors could be enriched under non-adherent, serumfree and sphere-forming conditions. These CD90 þ cells possess a higher ability to initiate tumor in vivo and could re-establish the cellular hierarchy of tumors from singlecell implantation, demonstrating their self-renewal properties. Interestingly, higher proportion of CD90 þ cells correlates with higher in vivo tumorigenicity of gastric primary tumor models. In addition, it was found that ERBB2 was overexpressed in about 25% of the gastric primary tumor models, which correlates with the higher level of CD90 expression in these tumors. Trastuzumab (humanized anti-ERBB2 antibody) treatment of hightumorigenic gastric primary tumor models could reduce the CD90 þ population in tumor mass and suppress tumor growth when combined with traditional chemotherapy. Moreover, tumorigenicity of tumor cells could also be suppressed when trastuzumab treatment starts at the same time as cell implantation. Therefore, we have identified a CSC population in gastric primary tumors characterized by their CD90 phenotype. The finding that trastuzumab targets the CSC population in gastric tumors suggests that ERBB2 signaling has a role in maintaining CSC populations, thus contributing to carcinogenesis and tumor invasion. In conclusion, the results from this study provide new insights into the gastric tumorigenic process and offer potential implications for the development of anticancer drugs as well as therapeutic treatment of gastric cancers.

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Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer

Cited by 158 publications

References 22 publications

Evaluation of HER2-based biology in 1,006 cases of gastric cancer in a Japanese population

Evaluation of HER2-based biology in 1,006 cases of gastric cancer in a Japanese population

Is Her-2 Status in the Primary Tumor Correlated with Matched Lymph Node Metastases in Patients with Gastric Cancer Undergoing Curative Gastrectomy?

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

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