Abstract | PURPOSE: EXPERIMENTAL DESIGN: A monoclonal antibody against MMSET was developed and immunohistochemical staining of tissue microarrays (TMA) containing a large number of tumor samples (n = 3774) and corresponding normal tissues (n = 904) was carried out. Further validations of MMSET expression were carried out on independent, tumor-specific sets of TMAs for urinary bladder (n = 1293) and colon cancer (n = 1206) with corresponding clinicopathological data and long-term follow-up. RESULTS: MMSET protein was highly expressed in different tumor types compared to normal counterparts. Particular frequent and/or high MMSET expression was found in carcinomas of the gastrointestinal tract (stomach, colon, anal canal), small cell lung carcinoma, tumors of the urinary bladder, female genitals, and skin. In bladder cancer, MMSET expression correlated with tumor aggressiveness. In contrast, MMSET expression was associated with good prognostic factors in colon cancer and was more pronounced in early stages of colon carcinogenesis (dysplasias) than in adenocarcinomas. However, colon cancer patients with high MMSET levels showed a worse 5-year survival. CONCLUSIONS: Our data suggest that MMSET has a broader role in cancer than previously anticipated, and further analysis might qualify it as a prognostic marker and a target for the development of therapy against several types of cancer.
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Authors | Heidi Rye Hudlebusch, Eric Santoni-Rugiu, Ronald Simon, Elisabeth Ralfkiær, Henrik Holm Rossing, Jens Vilstrup Johansen, Mette Jørgensen, Guido Sauter, Kristian Helin |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 17
Issue 9
Pg. 2919-33
(May 01 2011)
ISSN: 1557-3265 [Electronic] United States |
PMID | 21385930
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | ©2011 AACR. |
Chemical References |
- Antibodies, Monoclonal
- Oncogene Proteins
- Repressor Proteins
- Histone Methyltransferases
- Histone-Lysine N-Methyltransferase
- NSD2 protein, human
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Topics |
- Animals
- Antibodies, Monoclonal
(biosynthesis)
- Antibody Specificity
- Female
- Gene Expression Regulation, Enzymologic
- Gene Expression Regulation, Neoplastic
- Histone Methyltransferases
- Histone-Lysine N-Methyltransferase
(genetics, immunology, metabolism)
- Humans
- Male
- Mice
- Models, Biological
- Neoplasms
(genetics, metabolism)
- Oncogene Proteins
(genetics, metabolism)
- Repressor Proteins
(genetics, immunology, metabolism)
- Tissue Array Analysis
- Tumor Cells, Cultured
- Up-Regulation
(genetics)
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