Low cytoplasmic and nuclear KPNA2 expression in radiotherapy-treated head and neck squamous cell cancer is associated with an adverse outcome

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...

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Published in:	International journal of clinical and experimental pathology Vol. 8; no. 12; pp. 15814 - 15824
Main Authors:	Erben, Pia B, Brunner, Kathrin, Hecht, Markus, Haderlein, Marlen, Büttner-Herold, Maike, Agaimy, Abbas, Fietkau, Rainer, Hartmann, Arndt, Distel, Luitpold V
Format:	Journal Article
Language:	English
Published:	United States e-Century Publishing Corporation 01-01-2015
Subjects:	alpha Karyopherins - analysis Biomarkers, Tumor - analysis Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - radiotherapy Carcinoma, Squamous Cell - secondary Cell Nucleus - chemistry Chemoradiotherapy, Adjuvant Cytoplasm - chemistry Disease-Free Survival Down-Regulation Female Head and Neck Neoplasms - chemistry Head and Neck Neoplasms - mortality Head and Neck Neoplasms - pathology Head and Neck Neoplasms - radiotherapy Humans Immunohistochemistry Kaplan-Meier Estimate Male Middle Aged Multivariate Analysis Neoadjuvant Therapy - adverse effects Neoadjuvant Therapy - mortality Neoplasm Recurrence, Local Original Predictive Value of Tests Proportional Hazards Models Radiotherapy, Adjuvant Risk Factors Squamous Cell Carcinoma of Head and Neck Time Factors Tissue Array Analysis Treatment Outcome prognostic marker head and neck cancer KPNA2 Radiotherapy HNSCC
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Summary:	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. 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. 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. The combination of nuclear and cytoplasmic KPNA2 expression is a potential excellent prognostic parameter in HNSCC treated with radio(chemo)therapy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Equal comtributors.
ISSN:	1936-2625