期刊
APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
卷 17, 期 1, 页码 57-67出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/PAI.0b013e3181816ae2
关键词
c-MET; monoclonal antibody; ovarian cancer; glioma; molecular diagnostics; immunohistochemistry
资金
- Van Andel Research Institute
- Michigan Life Sciences Corridor
- Prostate [P50 CA97186]
- Ovarian SPORE [P50 CA083636]
- NATIONAL CANCER INSTITUTE [R01CA111882, P50CA083636, P50CA097186] Funding Source: NIH RePORTER
- MRC [G0800025] Funding Source: UKRI
- Medical Research Council [G0800025] Funding Source: researchfish
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.
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