Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kamal, NS; Soria, JC; Mendiboure, J; Planchard, D; Olaussen, KA; Rousseau, V; Popper, H; Pirker, R; Bertrand, P; Dunant, A; Le Chevalier, T; Filipits, M; Fouret, P; International Adjuvant Lung Trial-Bio investigators.
MutS homologue 2 and the long-term benefit of adjuvant chemotherapy in lung cancer.
Clin Cancer Res. 2010; 16(4): 1206-1215.
Doi: 10.1158/1078-0432.CCR-09-2204
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- Popper Helmuth
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- Abstract:
- Purpose: We sought to determine the long-term (median follow-up, 7.5 years) predictive power of human MutS homologue 2 (MSH2) immunohistochemical expression in patients who enrolled in the International Adjuvant Lung Trial. Experimental design: We tested the interaction between MSH2 and the allocated treatment (chemotherapy versus observation) in a Cox model adjusted on clinicopathologic variables. The significance level was set at 0.01. Results: MSH2 levels were low in 257 (38%) and high in 416 (62%) tumors. The benefit from chemotherapy was likely different according to MSH2 (interaction test, P = 0.06): there was a trend for chemotherapy to prolong overall survival when MSH2 was low [hazard ratio (HR), 0.76; 95% confidence interval (95% CI), 0.59-0.97; P = 0.03], but not when MSH2 was high (HR, 1.12; 95% CI, 0.81-1.55; P = 0.48). In the control arm, the HR was 0.66 (95% CI, 0.49-0.90; P = 0.01) when MSH2 was high. When combining MSH2 with excision repair cross-complementing group 1 (ERCC1) into four subgroups, the benefit of chemotherapy decreased with the number of markers expressed at high levels (P = 0.01). A similar decrease was noted when combining MSH2 and P27 (P = 0.01). Chemotherapy prolonged overall survival in the combined low MSH2/low ERCC1 subgroup (HR, 0.65; 95% CI, 0.47-0.91; P = 0.01) and in the combined low MSH2/low P27 subgroup (HR, 0.65; 95% CI, 0.46-0.93; P = 0.01). Conclusions: MSH2 expression is a borderline significant predictor of a long-term benefit from adjuvant cisplatin-based chemotherapy in patients with completely resected lung cancer. MSH2 combined with ERCC1 or P27 may identify patients most likely to benefit durably from chemotherapy. Clin Cancer Res; 16(4); 1206-15. (C) 2010 AACR.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
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- DNA-Binding Proteins - agonists
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- Humans -
- Lung Neoplasms - classification
- Male -
- Middle Aged -
- MutS Homolog 2 Protein - metabolism
- Prognosis -
- Proliferating Cell Nuclear Antigen - metabolism
- Tumor Markers, Biological - administration and dosage