Prognostic Implications of Altered Human Epidermal Growth Factor Receptors (HERs) in Gastric Carcinomas: HER2 and HER3 Are Predictors of Poor Outcome

Begnami, Maria D.; Fukuda, Emy; Fregnani, José Humberto Tavares Guerreiro; Nonogaki, Suely; Montagnini, André L.; Costa, Wilson Luiz da; Soares, Fernando Augusto

doi:10.1200/jco.2010.33.6313

Cited by 219 publications

(182 citation statements)

References 66 publications

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“…In this study, the HER2-positive patients not treated with trastuzumab showed survival rates similar to those of the HER2-negative patients. By contrast, the majority of previous studies have found poorer survival among patients with HER2-positive gastric cancer than among patients with HER2-negative tumors [9,15,16]. Most of these studies have been based on retrospective analyses in a single institution that combined patients with advancedstage cancer and those with resected gastric cancer.…”

Section: Discussionmentioning

confidence: 90%

“…Similarly, the prognostic value of HER2 status in gastric cancer has been evaluated in a number of reports. Although recent studies of gastric cancer have shown no impact of HER2 on survival [13,14], the majority of the past studies have suggested that HER2-positive gastric cancer was associated with a poorer prognosis than HER2-negative gastric cancer [9,15,16].…”

Section: Introductionmentioning

confidence: 99%

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Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment

et al. 2012

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Background The purpose of this study was to evaluate the impact of human epidermal growth factor receptor 2 (HER2) status and trastuzumab treatment on the prognosis of patients with advanced gastric cancer (AGC). Methods We retrospectively analyzed 364 AGC patients who received systemic chemotherapy. To evaluate the impact of trastuzumab exposure during any type of chemotherapy, our analysis used time-varying covariates to avoid a possible lead-time bias. Results Among the 364 patients, 58 (15.9 %) were HER2-positive. The median overall survival of the HER2-positive patients treated with trastuzumab (n = 43) was significantly longer than that of the HER2-negative patients [n = 306; 24.7 vs. 13.9 months, with an adjusted hazard ratio (HR) of 0.58; 95 % confidence interval (CI), 0.36-0.95; P = 0.03]. Notably, 22 patients continued with trastuzumab beyond the date of progression. By contrast, the HER2-positive patients not treated with trastuzumab (n = 15) showed survival similar to that of the HER2-negative patients (13.5 vs. 13.9 months, with an adjusted HR of 1.04; 95 % CI, 0.52-2.11; P = 0.91). According to the multivariate analysis, exposure to trastuzumab was independently associated with a better prognosis (HR 0.56; 95 % CI; 0.33-0.93; P = 0.026). Conclusions Recent HER2-positive AGC patients have a better prognosis than HER2-negative patients, particularly when treated with trastuzumab.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment

et al. 2012

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“…Thus, molecular pathology may be helpful to understand the disease pathogenesis and provide useful prognostic molecular markers. Potential biologic prognostic markers include overexpression of 14-3-3o, VEGF, mesothelin, EGF receptor, and elevated plasma level of osteopontin (6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Increased Guanine Nucleotide Exchange Factor Vav3 Expression in Human Gastric Cancer

Lin

Wang

Hseu

et al. 2012

Molecular Cancer Research

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Although gastric cancer is one of the most common malignancies worldwide, little is known on the molecular process of its development and progression. This study investigates the involvement of guanine nucleotide exchange factor Vav3 in tumor progression and in the prognosis of human gastric cancer. The two patient cohorts in this study consisted of 167 gastric cancer cases from 1997 through 2001, documenting pathologic and clinical factors, as well as the clinical outcomes. Immunohistochemistry, reverse transcription PCR, immunoblotting, and immunofluorescence were used to examine Vav3 expression in tumor and nontumor pairs of gastric tissues and gastric cell lines. Small hairpin RNA (shRNA) technology was used to study the effects of Vav3 knockdown on the growth and spread of gastric cancer cells. Finally, xenograph proliferation was used to study the tumor growth. Overexpression of Vav3 was associated with the depth of invasion (P ¼ 0.0004), nodal status (P ¼ 0.0260), distant metastasis (P ¼ 0.0003), stage (P ¼ 0.0002), and vascular invasion (P ¼ 0.0286); and correlated with poor disease-free survival (P < 0

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“…Although the criteria for EGFR amplification are not formally established and a wide range of EGFR/CEN7 ratios (1.7-6.0) were used in previous studies [3,5,22,24,26,29,30], the frequency of EGFR amplification did not vary among these studies, which may be attributed to the fact that the EGFR/CEN7 ratio is [10.0 in most patients with EGFR amplification, and a defined cutoff value would not influence the results (Fig. 2).…”

Section: Discussionmentioning

confidence: 90%

“…However, the incidence of EGFR overexpression reported in previous studies varies from 2 % to 81 %, probably the result of differences in antibodies, scoring systems, and observers [4,21,[24][25][26][27][28][29][30][31][32]. In contrast, the frequency of EGFR gene amplification in gastric cancers is consistently less variable (2-7 %), although most of these studies lacked a sufficiently large number of patients or a detailed EGFR GCN examination [3,5,22,24,26,29,30]. The correlation between overexpression and EGFR GCN has not been firmly established.…”

Section: Introductionmentioning

confidence: 84%

Gene copy number gain of EGFR is a poor prognostic biomarker in gastric cancer: evaluation of 855 patients with bright-field dual in situ hybridization (DISH) method

et al. 2014

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Background EGFR overexpression is a prognostic biomarker and is expected to be a predictive biomarker for anti-EGFR therapies in gastric cancer. However, few studies have reported the clinical impact of EGFR gene copy number (GCN) and its correlation with EGFR overexpression. Methods We used dual in situ hybridization (DISH) to detect EGFR GCN and chromosome 7 centromere (CEN7) in a set of tissue microarrays representing 855 patients with gastric cancer. These data were compared with those of immunohistochemical (IHC) analysis of EGFR expression to evaluate prognostic value. Results EGFR GCN gain (C2.5 EGFR signals per cell) was detected in 194 patients (22.7 %) and indicated poor prognosis. Among 194 patients, EGFR amplification (EGFR/CEN7 C 2.0) was observed in 29 patients (14.9 %), which was almost identical to the IHC 3? subgroup and worst prognostic subgroup. Patients with EGFR GCN gain but not amplification, including those exhibiting polysomy, also exhibited poorer prognosis than GCN nongain patients and were distributed between IHC 0/1? and 2? subgroups. GCN gain was frequently observed in patients with more advanced disease, but served as an independent prognostic factor regardless of the pathological stage. Conclusions EGFR GCN gain is a more accurate prognostic biomarker than EGFR overexpression in patients with gastric cancer.

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Prognostic Implications of Altered Human Epidermal Growth Factor Receptors (HERs) in Gastric Carcinomas: HER2 and HER3 Are Predictors of Poor Outcome

Cited by 219 publications

References 66 publications

Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment

Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment

Clinical Significance of Increased Guanine Nucleotide Exchange Factor Vav3 Expression in Human Gastric Cancer

Gene copy number gain of EGFR is a poor prognostic biomarker in gastric cancer: evaluation of 855 patients with bright-field dual in situ hybridization (DISH) method

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