Comparative Study on Overexpression of HER2/neu and HER3 in Gastric Cancer

Zhang, Xiu Li; Yang, Yun; Xu, Danyan; Qu, Jian Hui; Guo, Ming; Gong, Yan; Huang, Jin

doi:10.1007/s00268-009-0142-z

Cited by 147 publications

(122 citation statements)

References 47 publications

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“…Wang et al, 10 Marx et al, 15 Song et al, 30 Garcia et al, 31 Ghaderi et al, 36 Oshima et al, 38 Allgayer et al 39 Wang et al, 10 Marx et al, 15 Zhang et al, 18 Potrc et al, 23 Garcia et al, 31 Ghaderi et al, 36 Wang et al, 37 Allgayer et al 39 Zhang et al, 18 Yu et al, 19 Potrc et al, 23 Park et al, 24 Lee et al, 32 Pinto-de-Sousa et al, 34 Ghaderi et al, 36 Allgayer et al 39 [11 Studies (3 studies between 1990 and 1999 not displayed)]…”

Section: Tumor Gradementioning

confidence: 99%

“…III/IV Wang et al, 10 Zhang et al, 18 Im et al, 27 Ghaderi et al, 36 Allgayer et al 39 [5 Studies] Presence of microvascular invasion Wang et al, 10 Pinto-de-Sousa et al, 34 Allgayer et al 39 [3 Studies] Grabsch et al, 11 Barros-Silva et al, 16 Park et al, 24 Garcia et al 31 [8 Studies (4 studies between 1990 and 1999 not displayed)]…”

Section: Presence Of Metastases (M)mentioning

confidence: 99%

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Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review

Chua

Merrett

2011

Intl Journal of Cancer

162

111

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With the availability of a therapeutic target and an effective agent in trastuzumab, a systematic examination of the literature to investigate the role of human epidermal growth factor 2 (HER2) as a prognostic factor for survival and its association with clinicopathologic markers may improve treatment. An electronic search of the MEDLINE and PubMed databases (January 1990 to January 2011) was undertaken to identify translational studies that correlated HER2 with clinicopathologic markers and/or survival outcome. This review included 49 studies totaling 11,337 patients. Forty-four percent of patients had Stage I/II, and 56% had Stage III/IV disease. Immunohistochemistry was most commonly used to assess HER2 expression, identifying a median rate of 18% (range, 4-53%) of gastric cancer demonstrating HER2 overexpression. In patients with and without HER2 overexpression, the median 3-year disease-free survival rate was 58% (range, 50-88%) and 86% (range, 62-97%), respectively. Of the 35 studies reporting the impact of HER2 overexpression on survival, 20 studies (57%) reported no difference in overall survival, two studies (6%) reported significantly longer overall survival in patients with HER2 overexpression and 13 studies (37%) reported significantly poorer overall survival in patients with HER2 overexpression. The median overall survival and 5-year survival rate was 21 (range, 10-57) months and 42%, and 33 (range, 13-80) months and 52% in patients with and without HER2 overexpression, respectively. HER2 overexpression appears to be associated with poorer survival and with intestinal-type gastric cancer in this group of patients for whom majority undergone curative gastrectomy.On a global scale, gastric cancer remains the second most common cause of cancer-related death with an estimated 930,000 new cases diagnosed each year albeit an overall decline in incidence. 1 Noncardia gastric cancers have steadily declined. However, it has been observed that proximal gastric cancers (cardia and oesophago-gastric tumors) are increasing at a rate of up to 10% per year, far exceeding that of any other type of cancer. Metastatic or advanced unresectable gastric cancer is an aggressive malignancy with a poor prognosis despite chemotherapy treatment with median survival of 7.5 to 12 months and a median survival of 3 to 5 months if managed by best supportive care. 2 Gastric cancer is a chemosensitive disease where a range of chemotherapy agents may achieve response rates of 30 to 40%; however, in the advanced setting, the disease is limited by a low complete response rate and the response duration is protracted often leading to disease progression and treatment related toxicities. 3 Combination chemotherapy with a Japanese standard doublet of fluoropyrimidine and platinum or western triplet regimens has shown better response rates and outcomes over single agent chemotherapy. However, there remains no established global standard for treatment.The human epidermal growth factor 2 (HER2) gene is a proto-oncogene where high amplifica...

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Section: Tumor Gradementioning

confidence: 99%

Section: Presence Of Metastases (M)mentioning

confidence: 99%

Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review

Chua

Merrett

2011

Intl Journal of Cancer

162

111

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“…HER3 overexpression served as a poor prognostic factor in this study. In another study that evaluated gastric cancer tissues from patients who underwent curative surgery, it was noted that when EGFR and HER2 receptors were blocked, HER3 activity was upregulated [23]. The role of HER3 in the progression of malignancy has also been tested in breast cancer.…”

Section: Her Family Receptors and Gastric Cancermentioning

confidence: 99%

Section: Her Family Receptors and Gastric Cancermentioning

confidence: 99%

“…The different histological types of gastric cancer such as intestinal and diffuse types have been shown to overexpress both HER2 and HER3 [23]. Intestinal type has predominance of HER2 overexpression over HER3, while diffuse type has increased overexpression of HER3 compared to HER2 [23]. In a study where gastrectomy samples were obtained from 134 patients with gastric adenocarcinomas, HER3 overexpression was significantly correlated with increased depth of tumor invasion, involved lymph nodes, distant metastasis, more advanced tumor stage, and increase in recurrent disease [24].…”

Section: Her Family Receptors and Gastric Cancermentioning

confidence: 99%

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Targeting of HER Family Signaling Pathways in Gastric Cancer

Perkins¹

2014

Chemotherapy

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HER‐2/neu gene amplification in relation to expression of HER2 and HER3 proteins in patients with esophageal adenocarcinoma

Yoon

Sukov

Sattler

et al. 2013

Cancer

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BACKGROUND Human epidermal growth factor receptor 2 (HER2) is a therapeutic target in patients with esophageal adenocarcinoma (EAC), with gene amplification used as a selection criterion for treatment, although to the authors’ knowledge the concordance between amplification and HER2 protein expression remains undefined in EAC. Furthermore, the association between HER2 and its interacting partner, human epidermal growth factor receptor 3 (HER3), is unknown yet appears to be of potential therapeutic relevance. METHODS Patients with untreated EACs (N 5 673) were analyzed for HER2 amplification and polysomy 17 by fluorescence in situ hybridization in parallel with immunohistochemistry (IHC) (IHC scores of 0–1+, 2+, and 3+). Amplification was defined as HER2=CEP17 ≥2. HER3 expression by IHC was analyzed in randomly selected cases (n 5 224). IHC and fluorescence in situ hybridization results were compared using least squares linear regression. RESULTS Overall, 17% of the EACs (116 of 673 EACs) were HER2-amplified with an amplification frequency that was highest among IHC3+ cases (89%) and declined among IHC2+ cases (13%) and IHCO to IHC1+ cases (4%). Among HER2-amplified cases, the level of amplification increased linearly with HER2 membranous expression (HER2/CEP17 ratio: 7.9 in IHC3+ and 5.5 in IHC2+ vs 2.8 in IHCO to IHC11 [P<.0001]), with 14% of amplified tumors demonstrating absent/faint expression (IHCO to IHC1+). Polysomy 17 was not found to be associated with HER2 expression. Cytoplasmic HER3 expression was detected in 87% of tumors (195 of 224 tumors) and was found to be significantly associated with better differentiation (P<.0001). Stepwise increases in HER3 expression were associated with higher HER2 expression levels (P = .0019). CONCLUSIONS Levels of HER2 protein expression and amplification were found to be linearly associated and highly concordant. Among amplified tumors with absent/faint expression, the level of amplification was low. Frequent expression of HER3 suggests its relevance as a therapeutic target, and its significant association with HER2 supports ongoing efforts to inhibit HER2/HER3 in patients with EAC.

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Comparative Study on Overexpression of HER2/neu and HER3 in Gastric Cancer

Cited by 147 publications

References 47 publications

Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review

Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review

Targeting of HER Family Signaling Pathways in Gastric Cancer

HER‐2/neu gene amplification in relation to expression of HER2 and HER3 proteins in patients with esophageal adenocarcinoma

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