A Novel Multipurpose Monoclonal Antibody for Evaluating Human c-Met Expression in Preclinical and Clinical Settings

被引:37
作者
Knudsen, Beatrice S. [2 ,3 ]
Zhao, Ping [1 ]
Resau, James [1 ]
Cottingham, Sandra [4 ]
Gherardi, Ermanno [6 ]
Xu, Eric [1 ]
Berghuis, Bree [1 ]
Daugherty, Jennifer [1 ]
Grabinski, Tessa [1 ]
Toro, Jose [1 ]
Giambernardi, Troy [1 ]
Skinner, R. Scot [5 ]
Gross, Milton [5 ]
Hudson, Eric [1 ]
Kort, Eric [1 ]
Lengyel, Ernst [7 ]
Ventura, Aviva [2 ]
West, Richard A. [1 ]
Xie, Qian [1 ]
Hay, Rick [1 ]
Woude, George Vande [1 ]
Cao, Brian [1 ]
机构
[1] Van Andel Res Inst, Grand Rapids, MI 49503 USA
[2] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA
[3] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA
[4] Spectrum Hlth Hosp, Dept Pathol, Grand Rapids, MI USA
[5] Nucl Med Serv, Dept Vet Affairs Healthcare Syst, Ann Arbor, MI USA
[6] MRC Lab Mol Biol, Cambridge, England
[7] Univ Chicago, Dept Obstet & Gynecol, Gynecol Oncol Sect, Chicago, IL 60637 USA
关键词
c-MET; monoclonal antibody; ovarian cancer; glioma; molecular diagnostics; immunohistochemistry; HEPATOCYTE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; SMALL-MOLECULE INHIBITOR; CELL LUNG-CANCER; PROSTATE-CANCER; SCATTER FACTOR; FACTOR/SCATTER FACTOR; PROGNOSTIC-FACTOR; BREAST-CANCER; PROTEIN;
D O I
10.1097/PAI.0b013e3181816ae2
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
The inappropriate expression of the c-MET cell surface receptor in many human solid tumours necessitates the development of companion diagnostics to identify those patients who could benefit from c-MET targeted therapies. Tumor tissues are formalin fixed and paraffin embedded (FFPE) for histopathologic evaluation, making the development of an antibody against c-MET that accurately and reproducibly detects the protein in FFPE samples an urgent need. We have developed a monoclonal antibody (mAb), designated MET4, from a panel of MET-avid mAbs, based oil its specific staining pattern in FFPE preparations. The accuracy of MET4 immunohistochemistry (MET4-IHC) was assessed by comparing MET4-IHC in FFPE cell pellets with immunoblotting analysis. The technical reproducibility of MET4-IHC possessed a percentage coefficient of variability of 6.25% in intra-assay and interassay testing. Comparison with other commercial c-MET antibody detection reagents demonstrated equal specificity and increased sensitivity for c-MET detection in prostate tissues. In cohorts of ovarian cancers and gliomas, MET4 reacted with ovarian cancers of all histologic subtypes (strong staining in 25%) and with 63% of gliomas. In addition, MET4 bound c-MET oil the surfaces of cultured human cancer cells and tumor xenografts. In Summary, the MET4 mAb accurately and reproducibly measures c-MET expression by IHC in FFPE tissues and call be used for molecular imaging in vivo. These properties encourage further development of MET4 as a multipurpose molecular diagnostics reagent to help to guide appropriate selection of patients being considered for treatment with c-MET-antagonistic drugs.
引用
收藏
页码:57 / 67
页数:11
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