ERCC1, XPF and XPA—locoregional differences and prognostic value of DNA repair protein expression in patients with head and neck squamous cell carcinoma

Objectives Nucleotide excision repair protein expression has been claimed to be responsible for platinum-based chemotherapy resistance. ERCC1, XPF and XPA, core proteins in DNA repair, were evaluated regarding their prognostic value in patients with head and neck squamous cell carcinoma by looking a...

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Bibliographic Details
Published in:Clinical oral investigations 2019-08, Vol.23 (8), p.3319-3329
Main Authors: Prochnow, Sebastian, Wilczak, W., Bosch, V., Clauditz, T. S., Muenscher, A.
Format: Article
Language:English
Subjects:
Biomarkers, Tumor
Chemoresistance
Chemotherapy
Dentistry
DNA microarrays
DNA Repair
DNA-Binding Proteins - metabolism
Endonucleases - metabolism
ERCC1 protein
Female
Head & neck cancer
Humans
Male
Medicine
Multivariate analysis
Neoplasm Recurrence, Local
Nucleotide excision repair
Oral cavity
Original Article
Oropharynx
Platinum
Prognosis
Protein expression
Proteins
Squamous cell carcinoma
Squamous Cell Carcinoma of Head and Neck - metabolism
Tumors
Xeroderma Pigmentosum Group A Protein - metabolism
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Summary:Objectives Nucleotide excision repair protein expression has been claimed to be responsible for platinum-based chemotherapy resistance. ERCC1, XPF and XPA, core proteins in DNA repair, were evaluated regarding their prognostic value in patients with head and neck squamous cell carcinoma by looking at overall survival and time to recurrence. Materials and methods Tissue microarrays were constructed from 453 cases of HNSCC, including 222 oral (49%), 126 oropharyngeal (27.8%) and 105 laryngeal (23.2%) tumours. There were 284 XPF, 293 XPA and 294 ERCC1 specimens evaluable for protein expression analysis after immunohistochemical workup. Expression levels were dichotomised into high- and low-expressing groups. Outcomes for overall survival (OS) and time to recurrence (TTR) were analysed using the Kaplan-Meier method. Results No correlation between ERCC1, XPA and XPF expression and OS was found by looking at the overall patient cohort. However, subsite analysis revealed that high ERCC1 expression was associated with a significantly inferior OS in patients with SCC of the oral cavity ( p  = 0.028) and showed an independent predictive value in multivariate analysis ( p  = 0.0123). High XPA expression showed a significantly increased OS in patients with oropharyngeal SCC ( p  = 0.0386). Regarding XPF, no impact on OS in any subsite could be shown. Conclusions While high ERCC1 expression functions as a predictive marker with decreased OS in patients with squamous cell carcinoma of the oral cavity, high XPA expression shows an inverse effect in the subsite of the oropharynx, which has not been described previously. Clinical relevance ERCC1 and XPA might be candidates to overcome chemotherapy resistance in subtypes of HNSCC.
ISSN:1432-6981
1436-3771
DOI:10.1007/s00784-018-2751-0