The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas

Carneiro, Fátima; Sobrinho‐Simöes, Manuel

doi:10.1002/(sici)1097-0142(20000101)88:1<238::aid-cncr31>3.0.co;2-f

Cited by 26 publications

(24 citation statements)

References 4 publications

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“…12-14, 16, 26-32]. Earlier studies using Southern blot analysis or qPCR reported relatively high rates of MET amplification of approximately 10% (13,30,31), but recent studies using FISH or SISH found that MET amplification rates were lower, varying from 2% to 8% (12,26,27,29,31,32). In our study, the MET amplification rate was 7%, which is consistent with the 8% rate reported by An and colleagues who evaluated Chinese patients with locally advanced or metastatic gastric or gastroesophageal junction cancer using a similar FISH method (12).…”

Section: Discussionmentioning

confidence: 99%

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Peng

Gao

et al. 2015

Molecular Cancer Therapeutics

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MET and its sole ligand, hepatocyte growth factor (HGF), are promising targets in gastric and gastroesophageal junction cancer. We evaluated whether MET protein expression or MET gene amplification is prognostic for overall survival (OS) in Chinese patients with advanced gastric or gastroesophageal junction cancer. Archival formalin-fixed, paraffin-embedded tumor samples from patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancer enrolled in clinical trials at Peking University Cancer Hospital from 2008 to 2010 were assessed for MET and phospho-MET (p-MET) expression by immunohistochemistry and MET amplification by FISH. MET-positive expression was defined as membrane protein staining in !25% of tumor cells. MET amplification was defined as MET:centromere 7 ratio >2.0. We tested the association of MET status with clinical characteristics and OS, and also evaluated the association between expression and amplification. One hundred sixty-eight patients were eligible. Of the evaluable samples, 53 of 137 (39%) were MET positive, eight of 134 (6%) were p-MET positive, and eight of 113 (7%) were MET amplified. Neither MET expression nor MET amplification were associated with clinical characteristics, except Lauren classification (P ¼ 0.04); MET amplification was associated with diffuse type. No significant OS difference was observed between MET-positive and MET-negative populations, regardless of first-line chemotherapy received. In 95 evaluable patients, MET expression was significantly associated with MET amplification (P < 0.001); all MET-amplified tumor samples showed some MET expression. In 96 evaluable patients, p-MET positivity was significantly associated with MET amplification (P < 0.001). Further evaluation in larger and independent sample sets is warranted to confirm our findings.

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Section: Discussionmentioning

confidence: 99%

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Peng

Gao

et al. 2015

Molecular Cancer Therapeutics

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“…A multicenter phase II study of trastuzumab in combination with epirubicin and docetaxel was recently reported as first-line treatment for HER-2-overexpressing metastatic breast cancer (22)(23)(24). In UGCs, the rate of amplification and overexpression of ERBB2 usually varies between 8% and 28%, whereas amplification and expression of TOP2A seems to be more frequent (8,(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 88%

Molecular Dissection of 17q12 Amplicon in Upper Gastrointestinal Adenocarcinomas

Maqani

Belkhiri

Moskaluk

et al. 2006

Molecular Cancer Research

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DNA amplification at 17q is frequently detected in upper gastrointestinal adenocarcinomas (UGC; stomach and esophagus). In this study, we did fluorescence in situ hybridization on a tissue microarray that contained 304 UGCs and 89 normal stomach samples using a f168-kb BAC clone (CTD-2019C10) that maps to 17q12-q21.1. This 168-kb region contains the following genes: PPP1R1B/DARPP-32, STARD3, TCAP, PNMT, PERLD1, ERBB2, C17orf37, and GRB7 as well as the first two exons of ZNFN1A3. DNA amplification (z5 signals) was detected in 85 of 282 (30%) of UGCs, and high-level amplification (z10 signals) was seen in 28 of 282 (10%) of all tumors. Adenocarcinomas of gastroesophageal junction and lower esophagus had the highest frequency of amplification (45%) compared with stomach tumors (27%; P = 0.04). On the other hand, 38% of tumors with intestinal-type morphology had amplification compared with 26% of diffuse-type tumors (P = 0.02). We further did quantitative real-time reverse transcription-PCR on 74 frozen tissue samples from UGCs for 11 genes located within or adjacent to the boundaries of this f168-kb genomic region. These genes include all 9 genes that are fully or partially located inside the CTD-2019C10 clone as well as 2 additional adjacent genes (NEUROD and TOP2A). Overexpression of PPP1R1B/DARPP-32, TCAP, and TOP2A was seen in approximately half of the tumors, whereas STARD3 and ZNFN1A3 were rarely overexpressed (12%). Interestingly, there was a statistical correlation between expression of all 8 genes that map between PPP1R1B/DARPP-32 and GRB7, whereas expression of NEUROD, ZNFN1A3, and TOP2A that are partially inside or adjacent to the boundaries of the CTD-2019C10 clone did not correlate with the expression of any of these 8 genes. These data show a transcriptionally active oncogenomic region bounded by PPP1R1B/DARPP-32 and GRB7 in UGCs and provide further insight into expression levels of several critical genes. (Mol Cancer Res 2006;4(7):449 -55)

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“…On the other hand, c-met, a hepatocyte growth factor receptor modulating NF-B related to the extension of gastric cancer, is thought to be one of the prognostic factors in gastric cancer (Tacchini et al, 2000). Indeed, gastric cancers expressing c-met correlate with poor differentiation and prognosis (Carneiro and Sobrinho-Simoes, 2000;Nakajima et al, 1999). Together with the report that NF-B is up-regulated by the binding of hepatocyte growth factor to c-met, these reports suggest that heparanase may be up-regulated by signal transduction through the c-met pathway in heparanaseoverexpressing gastric cancers.…”

Section: Takaoka Et Almentioning

confidence: 99%

Heparanase Expression Correlates with Invasion and Poor Prognosis in Gastric Cancers

Takaoka

Naomoto

Ohkawa

et al. 2003

Laboratory Investigation

144

136

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SUMMARY:Degradation of basement membrane and extracellular matrix structures are important features of the metastatic process of malignant tumors. Human heparanase degrades heparan sulfate proteoglycans, which represent the main components of basement membranes and the extracellular matrix. Because of the role of heparanase in tumor invasion and metastasis, we examined heparanase expression in primary gastric cancers and in cell lines derived from gastric cancers by immunohistochemistry and RT-PCR, respectively. Four of seven gastric cancer cell lines showed heparanase mRNA expression by RT-PCR. Heparanase protein was detected in both the cytoplasm and the nucleus of heparanase mRNA-positive cells by immunohistochemical staining. Heparanase expression was confirmed in 35 (79.5%) of 44 gastric tumor samples by immunohistochemical staining. However, no or weak heparanase expression was detected in normal gastric mucosa. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Analysis of the clinicopathologic features showed stronger heparanase expression in cases of huge growing tumors, extensive invasion to lymph vessels, and regional lymph node metastasis. In gastric cancer, patients with heparanase expression showed significantly poorer prognosis than those without such expression (p ϭ 0.006). In conclusion, our findings suggest that high expression of heparanase in gastric cancer is a strong predictor of poor survival. (Lab Invest 2003, 83:613-622).

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The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas

Cited by 26 publications

References 4 publications

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Molecular Dissection of 17q12 Amplicon in Upper Gastrointestinal Adenocarcinomas

Heparanase Expression Correlates with Invasion and Poor Prognosis in Gastric Cancers

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