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

M. Gachechiladze, J. Škarda, V. Kolek, I. Grygárková, K. Langová, J. Bouchal, Z. Kolář, F. Baty, R. Stahel, W. Weder, A. Soltermann, M. Joerger,

. 2017 ; 105 (-) : 31-38. [pub] 20170118

Language English Country Ireland

Document type Journal Article, Multicenter Study

Persistent link   https://www.medvik.cz/link/bmc17031009

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.

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$a Gachechiladze, Mariam $u Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czechia. Electronic address: marjammg@gmail.com.
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$a 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.
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$a Škarda, Josef $u Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czechia.
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$a Kolek, Vítězslav $u Department of Tuberculosis and Respiratory Diseases, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czechia.
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$a Grygárková, Ivona $u Department of Tuberculosis and Respiratory Diseases, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czechia.
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$a Langová, Kateřina $u Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czechia.
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$a Bouchal, Jan $u Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czechia.
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$a Kolář, Zdeněk $u Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czechia.
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$a Baty, Florent $u Department of Pneumology, Cantonal Hospital, St. Gallen, Switzerland.
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$a Stahel, Rolf A., $u Clinic of Oncology, University Hospital, Zurich, Switzerland. $d 1950- $7 xx0280332
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$a Weder, Walter $u Department of Thoracic Surgery, University Hospital, Zurich, Switzerland.
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$a Soltermann, Alex $u Department of Pathology and Molecular Pathology, University Hospital, Zurich, Switzerland.
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$a Joerger, Markus $u Department of Medical Oncology and Hematology, Cantonal Hospital, CH-9007 St. Gallen, Switzerland. Electronic address: markus.joerger@kssg.ch.
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