title: Prognostic and predictive value of loss of nuclear RAD51 immunoreactivity in resected non-small cell lung cancer patients.
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Mariam
authors.initials: M
authors.lastname: Gachechiladze
authors.affiliation: Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czechia.
authors.forename: Josef
authors.initials: J
authors.lastname: Škarda
authors.affiliation: Department of Tuberculosis and Respiratory Diseases, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czechia.
authors.forename: Vítězslav
authors.initials: V
authors.lastname: Kolek
authors.affiliation: Department of Tuberculosis and Respiratory Diseases, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czechia.
authors.forename: Ivona
authors.initials: I
authors.lastname: Grygárková
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czechia.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Langová
authors.affiliation: Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czechia.
authors.forename: Jan
authors.initials: J
authors.lastname: Bouchal
authors.affiliation: Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czechia.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Kolář
authors.affiliation: Department of Pneumology, Cantonal Hospital, St. Gallen, Switzerland.
authors.forename: Florent
authors.initials: F
authors.lastname: Baty
authors.affiliation: Clinic of Oncology, University Hospital, Zurich, Switzerland.
authors.forename: Rolf
authors.initials: R
authors.lastname: Stahel
authors.affiliation: Department of Thoracic Surgery, University Hospital, Zurich, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Weder
authors.affiliation: Department of Pathology and Molecular Pathology, University Hospital, Zurich, Switzerland.
authors.forename: Alex
authors.initials: A
authors.lastname: Soltermann
authors.affiliation: Department of Medical Oncology and Hematology, Cantonal Hospital, CH-9007 St. Gallen, Switzerland. Electronic address: markus.joerger@kssg.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Joerger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004358:Drug Therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D051135:Rad51 Recombinase / Q000378:metabolism*; D011878:Radiotherapy; D019616:Thoracic Surgical Procedures; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C495153:RAD51 protein, human; D051135:Rad51 Recombinase
keywords: Chemotherapy; DNA repair; Non-small-cell lung cancer; RAD51