BackgroundEpidermal growth factor receptor family members such as ErbB1 and ErbB3 are involved in tumor progression and metastasis. Although, there are various reports about the prognostic value of EGFR members separately in gastric cancer, there is not any report about the probable correlation between ErbB1 and ErbB3 co-expression and gastric cancer prognosis. In present study, we assessed the correlation between ErbB1 and ErbB3 co-overexpression (in the level of mRNA and protein expression) and gastric cancer prognosis for the first time.MethodsErbB1 and ErbB3 expressions were analyzed by immunohistochemistry and real-time PCR in 50 patients with gastric cancer. Parametric correlations were done between the ErbB1 and ErbB3 expression and clinicopathological features. Multivariate and logistic regression analyses were also done to assess the roles of ErbB1 and ErbB3 in tumor prognosis and survival.ResultsThere were significant correlations between ErbB1/ErbB3 co-overexpression and tumor size (p = 0.026), macroscopic features (p < 0.05), tumor differentiation (p < 0.05), stage of tumor (p < 0.05), and recurrence (p < 0.05). Moreover, ErbB1/ErbB3 co-overexpression may predict the survival status of patients (p < 0.05).ConclusionErbB1 and ErbB3 co-overexpression is accompanied with the poor prognosis and can be used efficiently in targeted therapy of gastric cancer patients.

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Introduction: The epidermal growth factor receptors (EGFR) family stimulates a number of signal transduction cascades that regulate diverse cellular processes, such as proliferation, differentiation, survival, migration, and adhesion. These signaling pathways are important in normal cellular homeostasis but aberrant activation of the EGFR members can cause carcinogenesis. The carcinogenic role of HER3 and HER4 has been seen in gastric cancer. In this study, the prognostic effect of HER3 is evaluated in gastric cancer patients. Materials and Methods: Tumoral and free tumoral borders of gastric tissues were freshly obtained from 40 patients with primary gastric adenocarcinoma who underwent a surgical procedure. The patients who underwent gasterectomy did not get any neoadjuvant therapy. Histopathological features including tumor size, location, and grade of differentiation were defined and surgical stage was determined on the basis of the union international cancer TNM classification. RNA was extracted from normal and cancerous tissue of gastric samples using the RNeasy Mini kit (Qiagen, Hilden, Germany) and then the cDNA was synthesized by using synthesis kit (Fermentas, Lithuania) after that Quantitative Real-time PCR was performed by using SYBR green PCR master Mix (Fermentas, Lithuania) to evaluate the expression of HER3 in species. To determine the prognosis, we followed the patients’ situation for 6 and 12 months after surgery, then the correlation between HER3 (mRNA) and prognosis was determined. Statistical analysis was done by spss ver 19, for assessing the correlation between HER3 and clinicopathological factors used Independant sample T test and Kaplan-Meier curves were generated for overall survival, statistical significance was determined using Log-rank test. Results: 77.5% of patients were male and 22.5% were female, 52.5% of patients were older than 65 years whereas, 47.5% were less than 65. 35% of patients have HER3 over expression. HER3 expression was significantly associated with factors involved with tumor progression, including depth of tumor T1-T2 (P=0.000); involved lymph nodes (P=0.001); stage (P=0.000); recurrent disease (P=0.000); and CA 19-9 (P=0.000). The significant relationship between mRNA and protein of HER3 was seen.(P=0.000) HER3 over expression was associated with a significantly worse survival.(P=0.000) the protein of HER3 was an independent prognostic factor in the multivariate analysis, (P=0.007) 95% confidence interval was 0.006-0.454. Conclusion: HER3 is an independent prognostic factor which can cause tumor progression and poorer survival rate of patients, in cellular and molecular study is demonstrated that anti agents which target HER2 can cause compensatory over expression of HER3, so that, the unexpected result would be gained and prognosis would be poor, therefore, we suggest, assessing the expression HER3 in patients and use regime which target the band between HER2 and HER3 to get proper results and improve the prognosis. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C36. Citation Format: Mehrdad Soltani Delgosha, Yasha Makhdoumi. The prognostic effect of HER3 among gastric cancer patients. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C36.