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Prognostic and predictive value of loss of nuclear RAD51 immunoreactivity in resected non-small cell lung cancer patients

Journal Paper/Review - Jan 18, 2017

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Citation
Gachechiladze M, Škarda J, Kolek V, Grygárková I, Langová K, Bouchal J, Kolář Z, Baty F, Stahel R, Weder W, Soltermann A, Joerger M. Prognostic and predictive value of loss of nuclear RAD51 immunoreactivity in resected non-small cell lung cancer patients. Lung Cancer 2017; 105:31-38.
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Type
Journal Paper/Review (English)
Journal
Lung Cancer 2017; 105
Publication Date
Jan 18, 2017
Issn Print
Issn Electronic
1872-8332
Pages
31-38
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Brief description/objective

OBJECTIVES
In response to DNA damage, recombination proteins are relocalized into sub-nuclear complexes that are microscopically detected as RAD51-containing nuclear foci. We aimed for assessing the prognostic and predictive value of loss of nuclear RAD51 immunoreactivity ('RAD51 loss') in 2 independent stage I to III non-small cell lung cancer (NSCLC) patient cohorts undergoing surgical resection and eventual perioperative chemo-/radiotherapy (CT/RT).

MATERIALS AND METHODS
The discovery set included 69 evaluable patients (19 adenocarcinomas, ADC, 50 squamous cell carcinomas, SCC) from Palacky University Hospital, 45/69 (65.2%) with additional platinum-based CT. The replication set entailed 845 evaluable patients (446 ADC, 399 SCC) from University Hospital Zurich, 308/845 (36.5%) with platinum based CT or RT. RAD51 loss was defined as ≤20% of tumor cell nuclei having any nuclear RAD51 expression. We assessed the prognostic value of RAD51 loss in all patients and its predictive value in patients receiving CT/RT.

RESULTS
RAD51 loss was observed in 40/69 (58.0%) and 439/845 (51.9%) evaluable tumors in the discovery and replication set, respectively (p=0.34). It was more frequent in ADC compared to SCC (57.2% vs 47.4%, p=0.003). RAD51 loss was significantly associated with worse OS in both the discovery (adjusted HR=2.39, p=0.039) and replication set (adjusted HR=1.31, p=0.008). The unfavourable prognostic effect of RAD51 loss seen in the overall population was not observed in patients receiving perioperative CT (adjusted HR=1.07, p=0.73) or perioperative RT (adjusted HR=1.05, p=0.82).

CONCLUSION
RAD51 loss has an unfavourable prognostic impact in NSCLC patients undergoing curative surgical resection, but it may have a favourable predictive value in the subgroup of patients receiving perioperative platinum-based CT or RT, most likely as a consequence of deficient DNA repair.