Expression of epidermal growth factor receptor in gastric carcinomas

Takehana, Takuo; Kunitomo, Kazuyoshi; Suzuki, Shioto; Kono, Koji; Fujii, Hideki; Matsumoto, Yoshirô; Ooi, Akishi

doi:10.1016/s1542-3565(03)00219-2

Cited by 65 publications

(61 citation statements)

References 28 publications

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“…The frequencies of these gene amplifications were not significantly different from those previously reported for ERBB2, FGFR2, 9,10,12,14 MET, 6,7,14,15 and EGFR. 6,20 It is intriguing that, except for case 7, RTK gene amplification occurred in a mutually exclusive manner. Even in Case 7, RTK gene co-amplification did not occur in the same cells.…”

Section: Discussionmentioning

confidence: 99%

“…DNA from the cell lines MKN7, A431, KATOIII, HSC39, and MKN45, which were previously shown to display amplified ERBB2, EGFR, FGFR2, FGFR2 and MYC, and MET, respectively, were used as positive controls. 8,20 Multiplex ligation-dependent probe amplification analysis was performed by using two kits from MRCHolland. The SALSA MLPA KIT P175-A2 TumorGain kit contains two or three probes for each of 24 genes including ERBB2, EGFR, MET, MYC, CCND1, MDM2, and TOP2A.…”

Section: Multiplex Ligation-dependent Probe Amplificationmentioning

confidence: 99%

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Semi-comprehensive analysis of gene amplification in gastric cancers using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization

et al. 2015

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The prognosis of patients with gastric carcinomas at an advanced stage still remains dismal, and therefore novel therapeutic modalities are urgently needed. Since the successful targeting of amplified ERBB2 with a humanized monoclonal antibody, the amplified genes of other receptor tyrosine kinases such as EGFR, FGFR2, and MET, as well as those of other cell regulator genes, are being considered as candidate targets of molecular therapy. The aim of the present study was to determine the amplification status of 26 genes, which are frequently amplified in solid cancers, in advanced gastric cancers. A total of 93 formalin-fixed and paraffin-embedded advanced gastric cancer tissues were examined by multiple ligation-dependent probe amplification, and 32 cases with 'gain' or 'amplified' status of 16 genes were further examined for the respective gene amplification by fluorescence in situ hybridization (FISH) and for the respective protein overexpression by immunohistochemistry. The frequencies of gene amplifications in advanced gastric cancers were as follows: ERBB2 (13 cases, 14%), FGFR2 (7 cases, 8%), MYC (7 cases, 8%), TOP2A (7 cases, 8%), MET (4 cases, 4%), MDM2 (4 cases, 4%), CCND1 (3 cases, 3%), FGF10 (2 cases, 3%), and EGFR (1 case, 1%). Amplification of the receptor tyrosine kinases genes occurred in a mutually exclusive manner except for one tumor in which ERBB2 and FGFR2 were both amplified but in different cancer cells. Co-amplification of ERBB2 and MYC, and EGFR and CCND1, in single nuclei but on different amplicons, was confirmed in one case each. Attempts at correlating the FISH status with the immunohistochemical staining pattern showed variable results from complete concordance to no correlation. In conclusion, combination of multiple ligation-dependent probe amplification and FISH analysis is a feasible approach for obtaining the semi-comprehensive genetic information that is necessary for personalized molecular targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Multiplex Ligation-dependent Probe Amplificationmentioning

confidence: 99%

Semi-comprehensive analysis of gene amplification in gastric cancers using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization

et al. 2015

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“…Thus far, genetic alterations previously reported in gastric carcinomas include the amplification of the ERBB2, FGFR2, EGFR, MET and Myc genes and point/frameshift mutations of the KRAS, TP53, APC and mismatch repair genes. [1][2][3][4][5] The Myc located on 8q24 encodes a transcription factor that is likely to contribute to tumorigenesis via its upregulation, which would result in unrestrained cellular proliferation, blocking of differentiation, and promotion of genomic instability, including gene amplification, karyotypic abnormality, and hypersensitivity to DNA-damaging agents. 6,7 A number of alterations, including gene amplification, chromosomal translocation, insertional mutations, altered transcriptional elongation rates, and a prolonged mRNA half-life, 7 affect MYC expression in various neoplasms.…”

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confidence: 99%

“…12 Stimuli through these receptors, such as those initiated by high-affinity ligand binding, activate a cascade of biochemical and physiological responses that are relayed to transcription factors, resulting in changes in gene and protein expression. In our previous studies combining immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), we demonstrated that ERBB2 and EGFR are overexpressed in 8-10%, 4,13 and 10%, 3 respectively, of gastic cancers, due primarily to gene amplification.…”

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Non-incidental coamplification of Myc and ERBB2, and Myc and EGFR, in gastric adenocarcinomas

et al. 2007

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This study was conducted to assess the frequencies of protein overexpression and gene amplification of Myc and to identify the mechanisms of Myc gene amplification, especially with regards to its possible coamplification with ERBB2 or EGFR in gastric adenocarcinomas. By immunohistochemical analysis of a total of 300 formalin-fixed and paraffin-embedded gastric adenocarcinomas, the nuclear overexpression of MYC was found in 47 tumors (16%). A fluorescence in situ hybridization (FISH) analysis revealed that nine (19%) of the 47 tumors with protein overexpression had cancer cells with high levels of Myc amplification, whereas only seven (6%) of the 122 tumors without protein overexpression showed high-level Myc gene amplification. Such Myc amplification was significantly correlated with positive nuclear protein overexpression. The coamplification of ERBB2 or EGFR with Myc that was found in six and four cases, respectively, is believed to be nonincidental because those frequencies were significantly higher than the individual frequencies observed for the total examined cases (ERBB2: 7%; EGFR: 4%). The high levels of gene amplification of these three genes, as visualized by FISH, could be broadly classified into two typical types, namely, 'multiple scattered signals' and 'large clustered signals'. Using two-color FISH, the coexistence of coamplified Myc and ERBB2, or Myc and EGFR, within single nuclei in various combinations of amplification types and copy numbers, could be ascertained in all nine cases, including one in which the synchronous 'multiple scattered type' coamplification of Myc and ERBB2 was observed. In three tumors, coamplification of ERBB2 and EGFR was found; however, ERBB2-and EGFR-amplified cell populations were separate and mutually exclusive. We propose that the nonincidental coamplification of Myc and either ERBB2 or EGFR occurred through translocation and subsequent rearrangement.

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“…Overexpression of EGFR, as determined by immunohistochemistry (IHC), almost exclusively occurs by gene amplification and is associated with shorter survival [10,11]. Unfortunately, the IHC level of EGFR expression does not appear to hold promise as an appropriate marker for predicting response in patients receiving anti-EGFR mAbs.…”

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confidence: 99%