دورية أكاديمية
Isolated loss of PMS2 expression in colorectal cancers: Frequency, patient age, and familial aggregation
| العنوان: | Isolated loss of PMS2 expression in colorectal cancers: Frequency, patient age, and familial aggregation |
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| المؤلفون: | Gill, S., Lindor, N., Burgart, L., Smalley, R., Leontovich, O., French, A., Goldberg, R., Sargent, D., Jass, J., Hopper, J., Jenkins, M., Young, J., Barker, M., Walsh, M., Ruszkiewicz, A., Thibodeau, S. |
| المصدر: | http://dx.doi.org/10.1158/1078-0432.ccr-05-0661Test. |
| بيانات النشر: | Amer Assoc Cancer Research |
| سنة النشر: | 2005 |
| المجموعة: | The University of Adelaide: Digital Library |
| مصطلحات موضوعية: | Humans, Colorectal Neoplasms, DNA Repair Enzymes, Adaptor Proteins, Signal Transducing, Carrier Proteins, DNA-Binding Proteins, Neoplasm Proteins, Proto-Oncogene Proteins, Nuclear Proteins, Immunohistochemistry, Microsatellite Repeats, Adolescent, Adult, Aged, Middle Aged, Female, Male, MutS Homolog 2 Protein, Adenosine Triphosphatases, MutL Protein Homolog 1, Mismatch Repair Endonuclease PMS2 |
| الوصف: | © 2005 American Association for Cancer Research. ; Purpose: Most colorectal cancers that have high levels of microsatellite instability (MSI-H) show loss of immunohistochemical expression of proteins that participate in the DNA mismatch repair process, most often involving MLH1 and MSH2. Less commonly, a third DNA mismatch repair protein, MSH6, may also be lost as the primary event. Rarely, tumors with MSI-H show normal expression of these three proteins. The genetic deficiency leading to the MSI-H phenotype in such cases is unknown. PMS2 is another member of the DNA mismatch repair complex. Its expression is generally lost in tumors with MLH1 loss of expression. Rarely, there is selective loss of PMS2 expression. We sought to describe the frequency and clinical correlates of selective loss of expression of PMS2 with the MSI-H tumor phenotype. Experimental Design: Two thousand seven hundred nineteen colorectal cancers from both clinic- and research-based ascertainment were studied. Tumor MSI testing and immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 were conducted. Medical records were abstracted for age at diagnosis, gender, colorectal cancer site, and family history. Results: Five hundred thirty-five of the 2,719 tumors were MSI-H. Of these, 93% showed loss of expression of MLH1, MSH2, and/or MSH6. Thirty-eight showed normal expression for these proteins. PMS2 immunohistochemical staining was successful in 32 of 38 of these tumors. Of the 32, 23 showed selective loss of expression of PMS2. This was associated with young age of diagnosis and right-sided location but not with a striking family history of cancer. Conclusions: Overall, 97% of the MSI-H tumors showed loss of expression for one or more of these four mismatch repair proteins. Selective loss of expression of PMS2 was present in 72% of cases in which colorectal cancers had an MSI-H phenotype but no alteration of expression of MLH1, MSH2, and MSH6. The underlying mechanism involved cannot be determined from this study but could involve point ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1078-0432 1557-3265 |
| العلاقة: | Clinical Cancer Research, 2005; 11(18):6466-6471; http://hdl.handle.net/2440/55448Test; Young, J. [0000-0002-1514-1522]; Ruszkiewicz, A. [0000-0001-9052-4948] |
| DOI: | 10.1158/1078-0432.CCR-05-0661 |
| الإتاحة: | https://doi.org/10.1158/1078-0432.CCR-05-0661Test https://doi.org/10.1158/1078-0432.ccr-05-0661Test http://hdl.handle.net/2440/55448Test |
| رقم الانضمام: | edsbas.3478481B |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 10780432 15573265 |
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| DOI: | 10.1158/1078-0432.CCR-05-0661 |