[Frontiers in Bioscience E3, 1182-1191, June 1, 2011]

Prognostic value of H-MLH1 after adjusting for RPA class in GBM patients

Ali Choucair1, Jennifer Moughan2, Chris Schultz3, Alan Schulsinger4, Minesh Mehta5, Walter Curran6

1Intermountain Medical Center, 5171 South Cottonwood Street, Neuroscience Center, Suite 810, Murray, Utah 84107, 2Radiation Therapy Oncology Group, American College of Radiology, 1818 Market Street, Suite 1600, Philadelphia, Pa. 19103-3604, 3Department of Radiation Oncology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI 53226, 4SUNY, 339 Hicks Str, Brooklyn, N.Y. 11201, 5University of Wisconsin, Human Oncology/Radiation Oncology, 600 Highland Avenue K4/310-3684, Madison, WI 53792, 6Emory University School of Medicine, Radiation Oncology, 1365 Clifton Road NE Rm. A1316, Atlanta, GA 30322


1. Abstract
2. Introduction
3. Materials and methods
3.1. Immnohistochemistry (IHC)
3.2. Statistical methods
4. Results
5. Discussion
5.1. MMR
5.2. MGMT
5.3. p53
5.4. NER
6. Acknowledgements
7. References


Repair of DNA adducts appears to be an important mechanism in chemotherapy responsiveness in glioblastoma multiforme (GBM). Meta-analyses have suggested that the addition of chemotherapy increases the percentage of long-term survivors. Because GBM is characterized by multiplicity of pathways that characterize growth and treatment resistance, we hypothesized probing a multiplicity of repair factors may be able to identify more than one prognostic factor that may be utilized in molecularly targeted therapy that might improve survival and QOL. Seven DNA repair factors showed statistical significance when added to the initial logistic model of RPA class on length of survival status. After adjusting for RPA class the only statistically significant result of the multivariable logistic regressions for these 7 DNA repair factors was that as hMLH1-MF1 increased, the odds of being a short-term survivor versus a long-term survivor decreased (OR: 0.913, 95% CI: 0.838-0.995, p=0.0385), multivariable analysis showed no associations between survival status and MGMT and p53 status, and the only statistically significant prognostic DNA repair factor was human Mut L Homologue 1 (hMLH1).