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• W2898427593 abstract "Ribonucleotide reductase M1 (RRM1) is the catalytic subunit of ribunucleotide reductase, the enzyme responsible for de novo synthesis of most of the deoxyribonucleotides. Low-level expression of RRM1 has been associated to better prognosis in patients with solid tumors. A previous study identified that RRM1 is a predictor for freedom from recurrence in patients with malignant pleural mesothelioma (MPM) undergoing induction chemotherapy following extrapleural pneumonectomy. Ribonucleotide reductase subunit M2 (RRM2) is associated with apoptosis, cell proliferation, invasion and migration. Some studies have suggested that expression of RRM2 could play a role in tumorigenesis of several cancers; however, its role in MPM is unknown. The expression of RRM1 and RRM2 was assessed by immunohistochemistry using commercial antibodies. Quantitative analysis was performed using computerized image software, namely digital pathology. All of the samples were scanned and the median value of each marker was used as the cutoff value, >median value corresponds to high expression level and <median value to low expression level. The expression levels were determined in samples from 91 patients with advanced MPM, who had received gemcitabine-based chemotherapy. We correlated these data with clinical parameters and disease outcome (Progression Free Survival [PFS]). Our study population presented a median age of 60 years (53 -71 yrs), most were male 64.8 %, with asbestos exposure in 57.2% of cases and epithelioid histology in 85.7%. Almost half of the patients received gemcitabine as first-line treatment (n=43; 47.3%). Overall PFS was 14.1 months (95% CI 9.8–18.4 months,) while PFS in patients receiving gemcitabine treatment was 6.8 months (95% CI 5.4–8.2 months). Several factors were associated to an improved PFS, including female vs. male sex (7.2 vs 6.6 months, p=0.062) and epithelial vs. sarcomatoid histology (7.2 vs 3.8 months, p=0.035) after gemcitabine treatment in univariate analysis. In the multivariate analysis, sex (HR 3.06, p=0.085) and no wood-smoke exposure (HR 2.55, p=0.092) were independently associated to gemcitabine treatment. Patients with high expression levels of RRM1 showed better PFS compared to patients with low expression levels (7.6 vs 5.5 months, p=0.049) in univariate analysis; with a HR of 0.204 (0.050–0.831) p=0.026 in multivariate analysis. Conversely, the M2 subunit (RRM2) did not show any significant associations (7.6 vs 6.6 months, p=0.363). Our results suggest that high protein expression levels of RRM1 could potentially serve as a biomarker of response to gemcitabine treatment in patients with advanced stage MPM." @default.
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• W2898427593 date "2018-10-01" @default.
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• W2898427593 title "P2.06-26 Ribonucleotide Reductase Subunit M1 but not M2 is Associated to Better PFS in Patients with Advanced Stage Mesothelioma" @default.
• W2898427593 doi "https://doi.org/10.1016/j.jtho.2018.08.1281" @default.
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