Sebastian Prochnow1, W Wilczak2, V Bosch3, T S Clauditz2, A Muenscher3. 1. Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Building O 10, Martinistrasse 52, 20246, Hamburg, Germany. s.prochnow@uke.de. 2. Department of Pathology, University of Hamburg, Hamburg, Germany. 3. Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Building O 10, Martinistrasse 52, 20246, Hamburg, Germany.
Abstract
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.
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.
Entities:
Keywords:
DNA repair; ERCC1; HNSCC; Prognostic factors; XPA; XPF
Authors: J Bellmunt; L Paz-Ares; M Cuello; F L Cecere; S Albiol; V Guillem; E Gallardo; J Carles; P Mendez; J J de la Cruz; M Taron; R Rosell; J Baselga Journal: Ann Oncol Date: 2007-01-17 Impact factor: 32.976
Authors: L Bubendorf; J Kononen; P Koivisto; P Schraml; H Moch; T C Gasser; N Willi; M J Mihatsch; G Sauter; O P Kallioniemi Journal: Cancer Res Date: 1999-02-15 Impact factor: 12.701
Authors: Andy Trotti; Lisa A Bellm; Joel B Epstein; Diana Frame; Henry J Fuchs; Clement K Gwede; Eugene Komaroff; Luba Nalysnyk; Marya D Zilberberg Journal: Radiother Oncol Date: 2003-03 Impact factor: 6.280
Authors: David J Adelstein; Yi Li; George L Adams; Henry Wagner; Julie A Kish; John F Ensley; David E Schuller; Arlene A Forastiere Journal: J Clin Oncol Date: 2003-01-01 Impact factor: 44.544