Prognostic Value and Clinical Pathology of c-MET Expression and Amplification in Gastric Carcinoma

November 29, 2013 updated by: Ruihua Xu, Sun Yat-sen University

Prognostic Value and Clinical Pathology of c-MET Expression and Amplification in Gastric Carcinoma: the Comparison Between the Primary and Metastatic Lesions, Early Stage and Advanced Stage

The MET oncogene encodes the receptor tyrosine kinase (RTK) for hepatocyte growth factor (HGF) and controls genetic programs leading to cell growth, invasion and protec¬tion from apoptosis. Although the definitive role of MET oncogene is yet to be determined in carcinogenesis of gastric cancer, overexpression and amplification of c-Met has been demonstrated in gastric cancer cell lines. In addition, approximately 10-20% of gastric cancer tissues and up to 40% of the scirrhous histological subtype were shown to harbor increased MET gene copy numbers. Importantly, PHA-665,752, a selective c-Met kinase inhibitor showed significant reduction of established tumor mass in mouse xenografts with GTL16, a gastric cancer cell line with >10-fold MET amplification. Another pivotal study showed that gastric cancer cells with MET amplification were extremely sensitive to PHA-665,752 and implicated a potential role of c-Met protein in developing theranostics in gastric cancer. More and more data indicated that c-Met was an important prognostic factor in gastric cancer.

Gastric cancer is a heterogeneous disease. Does the expression and amplification of c-Met in the primary lesion differ from the metastatic disease? Does the expression and amplification of c-Met in the early disease differ from advanced disease? Till now there is no related report.

Purposes:

  • Compare the expression and amplification of c-Met between primary lesion and metastatic lesion together with clinical characteristic, to explore the relationship of c-Met expression and metastatic pattern
  • Compare the expression and amplification of c-Met between early stage and metastatic stage, and to explore the role of c-MET in the development of carcinoma

Study Overview

Status

Unknown

Conditions

Detailed Description

We retrospectively collect the metastatic gastric cancer patients who received a surgical resection of both primary diseases and metastatic lesions during January 2006 and December 2012. Patients are collected based on the following criteria: (1) pathology proven advanced gastric adenocarcinoma; (2) the paraffin-embedded tissues of the primary and metastatic lesions were available (3) full information of follow-up. There are 100 patients suitable for the analysis. c-MET protein expression and amplification are assessed in paraffin-embedded tissues of the primary and metastatic diseases obtained from 100 patients by immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH). The clinical pathologic data of the patients are also collected for analysis, including: gender, age, Karnofsky performance score (KPS), chemotherapy regimens, tumor locations, Lauren classification, histology subtypes, metastatic sites.

In order compare c-Met expression and amplification between early and advanced stage, we will match 100 early stage (stage I and stage II) patients based on the following criteria (1) pathology proven gastric adenocarcinoma with radical resection; (2) the paraffin-embedded tissues of the primary lesions is available (3) full information of follow-up MET IHC will employ the Dako MET IHC assay and supplied assay protocol and pathology scoring guideline.

MET FISH will also employ the Dako MET FISH assay supplied assay protocol and pathology scoring guideline.

Study Type

Observational

Enrollment (Actual)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-sen University Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

We retrospectively collect the metastatic gastric cancer patients who received a surgical resection of both primary diseases and metastatic lesions during January 2006 and December 2012. c-MET protein expression and amplification are assessed in paraffin-embedded tissues of the primary and metastatic diseases obtained from 100 patients by immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH). In order to compare c-Met expression and amplification between early and advanced stage, we will match 100 early stage (stage I and stage II) patients. MET IHC will employ the Dako MET IHC assay and supplied assay protocol and pathology scoring guideline.

Description

Inclusion Criteria:

  1. For metastatic gastric cancer patients (1) pathology proven advanced gastric adenocarcinoma; (2) the paraffin-embedded tissues of the primary and metastatic lesions were available; (3) full information of follow-up
  2. For early stage gastric cancer patients (1) pathology proven gastric adenocarcinoma with radical resection; (2) the paraffin-embedded tissues of the primary lesions is available; (3) full information of follow-up

Exclusion Criteria:

  1. Older than 70 years old or younger than 18 years old
  2. without paraffin-embedded tissue
  3. without information of follow-up

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Metastatic gastric cancer patients
Selecte 100 cases of eligible metastatic gastric cancer patients with primary and metastatic lesion (1:1). Use the immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH) to detect the status of C-met.
Early stage gastric cancer
Selected 100 cases of eligible gastric cancer patients with previously early stage gastric cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 2 years
From the diagnosis to the time of last follow up or death
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive rate of C-met
Time Frame: 8%
The positive rate of c-met in the primary and metastastic diseases and in different stage diseases patients
8%

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Rui-hua Xu, MD, PhD, Sun Yat-Sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Anticipated)

December 1, 2014

Study Completion (Anticipated)

December 1, 2014

Study Registration Dates

First Submitted

November 20, 2013

First Submitted That Met QC Criteria

November 29, 2013

First Posted (Estimate)

December 5, 2013

Study Record Updates

Last Update Posted (Estimate)

December 5, 2013

Last Update Submitted That Met QC Criteria

November 29, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C-met in gastric cancer
  • Amgen (Other Grant/Funding Number: Amgen)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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