title: Low cytoplasmic and nuclear KPNA2 expression in radiotherapy-treated head and neck squamous cell cancer is associated with an adverse outcome.
abstract: BACKGROUND
  KPNA2 has effects on carcinogenesis, cell differentiation and transcriptional regulation. KPNA2 has been linked to DNA damage repair by its role to import the DNA double strand break repair complex MRN into the nucleus. The aim of our study was to evaluate the prognostic value of KPNA2 expression in both cytoplasmic and nuclear location in patients with HNSCC treated with radio(chemo)therapy.
  
  
  METHODS
  225 patients with HNSCC treated with neoadjuvant, definitive or adjuvant radio(chemo)therapy were included. Immunohistochemical staining was performed on tissue micro arrays to evaluate nuclear and cytoplasmic KPNA2 expression.
  
  
  RESULTS
  The median fraction of tumor cells with nuclear KPNA2 expression was 15%. 47% of tumor samples showed positive cytoplasmic staining. Patients with low nuclear as well as negative cytoplasmic expression tended to have an unfavorable prognosis. There was no correlation between nuclear and cytoplasmic KPNA2 expression. Low nuclear combined with negative cytoplasmic KPNA2 had a clearly unfavorable prognostic effect in local failure-free survival (P=0.014), metastasis-free survival (P=0.001) and no evidence of disease (P=0.008). A combination of low nuclear/negative cytoplasmic with high nuclear/high cytoplasmic KPNA2 expression was prognostically unfavorable with regard to tumor specific survival (P=0.021) and to a lower extent to overall survival (P=0.18). In multivariate analysis low nuclear/negative cytoplasmic versus any high KPNA2 (P=0.008) and T-category (P=0.002) proved as independent prognostic variables.
  
  
  CONCLUSIONS
  The combination of nuclear and cytoplasmic KPNA2 expression is a potential excellent prognostic parameter in HNSCC treated with radio(chemo)therapy.
authors.affiliation: Institute of Pathology, The University Hospitals, Friedrich-Alexander-University of Erlangen-Nürnberg Erlangen, Germany.
authors.forename: Pia B
authors.initials: PB
authors.lastname: Erben
authors.affiliation: Institute of Pathology, The University Hospitals, Friedrich-Alexander-University of Erlangen-Nürnberg Erlangen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Brunner
authors.affiliation: Department of Radiation Oncology, The University Hospitals, Friedrich-Alexander-University of Erlangen-Nürnberg Erlangen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hecht
authors.affiliation: Department of Radiation Oncology, The University Hospitals, Friedrich-Alexander-University of Erlangen-Nürnberg Erlangen, Germany.
authors.forename: Marlen
authors.initials: M
authors.lastname: Haderlein
authors.affiliation: Institute of Pathology, The University Hospitals, Friedrich-Alexander-University of Erlangen-Nürnberg Erlangen, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Büttner-Herold
authors.affiliation: Institute of Pathology, The University Hospitals, Friedrich-Alexander-University of Erlangen-Nürnberg Erlangen, Germany.
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
authors.affiliation: Department of Radiation Oncology, The University Hospitals, Friedrich-Alexander-University of Erlangen-Nürnberg Erlangen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.affiliation: Institute of Pathology, The University Hospitals, Friedrich-Alexander-University of Erlangen-Nürnberg Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Radiation Oncology, The University Hospitals, Friedrich-Alexander-University of Erlangen-Nürnberg Erlangen, Germany.
authors.forename: Luitpold V
authors.initials: LV
authors.lastname: Distel
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D002467:Cell Nucleus / Q000737:chemistry*; D059186:Chemoradiotherapy, Adjuvant; D003593:Cytoplasm / Q000737:chemistry*; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000401:mortality; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D028901:alpha Karyopherins / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D028901:alpha Karyopherins; C087978:karyopherin alpha 2
keywords: HNSCC; KPNA2; Radiotherapy; head and neck cancer; prognostic marker; radiotherapy