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      Prognostic value of epidermal growth factor receptors in gastric cancer: a survival analysis by Weibull model incorporating long-term survivors

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          Abstract

          Background

          There is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer.

          Methods

          This retrospective study included 201 patients with gastric and esophagogastric junction adenocarcinoma stages 0–IV (AJCC 6th edition) who underwent primary tumor resection. Tissues from primary tumors were analyzed by tissue microarray technology and immunohistochemistry. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to the Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution.

          Results

          Membrane expression of HER1, HER2, and HER4 were 9, 17, and 15 %, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3, and HER4 were 45, 62, and 24 %, respectively. HER2 and HER3 expression were correlated ( p < 0.001) and associated with intestinal-type histology ( p = 0.001 and p < 0.001, respectively) and advanced age ( p = 0.011 and p = 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage, and receptor expressions, only TNM stage showed prognostic influence.

          Conclusions

          According to analysis by a parametric model, the EGFR family did not have prognostic influence in the gastric cancer population studied. The data presented showed a correlation between HER2 and HER3 expression, which might suggest a potential role for HER2–HER3 heterodimerization inhibitors.

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          Most cited references37

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          Tissue microarrays for high-throughput molecular profiling of tumor specimens.

          Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray. Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors.
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            Reporting recommendations for tumor marker prognostic studies.

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              Epidermal growth factor-related peptides and their receptors in human malignancies.

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                Author and article information

                Contributors
                +55-17-33216600 , +55-17-33216638 , jacome@usp.br
                Journal
                Gastric Cancer
                Gastric Cancer
                Gastric Cancer
                Springer Japan (Tokyo )
                1436-3291
                1436-3305
                28 February 2013
                28 February 2013
                2014
                : 17
                : 76-86
                Affiliations
                [ ]Department of Medical Oncology, Barretos Cancer Hospital, Str. Antenor Duarte Villela, 1331, Barretos, SP 14784-400 Brazil
                [ ]Department of Gastrointestinal Surgical Oncology, Barretos Cancer Hospital, Str. Antenor Duarte Villela, 1331, Barretos, SP 14784-400 Brazil
                [ ]Department of Pathology, Barretos Cancer Hospital, Str. Antenor Duarte Villela, 1331, Barretos, SP 14784-400 Brazil
                [ ]Center for Researcher Support, Barretos Cancer Hospital, Str. Antenor Duarte Villela, 1331, Barretos, SP 14784-400 Brazil
                [ ]Department of Social Medicine, School of Medicine, University of São Paulo at Ribeirão Preto, Av. Bandeirantes, 3900, 2nd Floor, Ribeirão Preto, SP 14049-900 Brazil
                [ ]Department of Surgery and Anatomy, School of Medicine, University of São Paulo at Ribeirão Preto, Av. Bandeirantes, 3900, 9th Floor, Ribeirão Preto, SP 14049-900 Brazil
                Article
                236
                10.1007/s10120-013-0236-z
                3889290
                23455716
                12bbda09-d41d-46e4-ab5f-c388079a51dc
                © The Author(s) 2013

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 7 November 2012
                : 3 January 2013
                Categories
                Original Article
                Custom metadata
                © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2014

                Oncology & Radiotherapy
                stomach neoplasms,epidermal growth factor receptor,her2,survival analysis,microarray analysis

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