title: The significance of tumoral ERCC1 status in patients with locally advanced cervical cancer treated with chemoradiation therapy: a multicenter clinicopathologic analysis.
abstract: OBJECTIVE
  ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters.
  
  
  METHODS
  A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years.
  
  
  RESULTS
  The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067).
  
  
  CONCLUSIONS
  In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis.
authors: Department of Oncology, University of Calgary, Calgary, AB, Canada. Corinne.Doll@albertahealthservices.ca
authors: Corinne M
authors: CM
authors: Doll
authors: Christina
authors: C
authors: Aquino-Parsons
authors: Melania
authors: M
authors: Pintilie
authors: Alexander C
authors: AC
authors: Klimowicz
authors: Stephanie K
authors: SK
authors: Petrillo
authors: Michael
authors: M
authors: Milosevic
authors: Peter S
authors: PS
authors: Craighead
authors: Blaise
authors: B
authors: Clarke
authors: Susan P
authors: SP
authors: Lees-Miller
authors: Anthony W
authors: AW
authors: Fyles
authors: Anthony M
authors: AM
authors: Magliocco
mesh_terms: D000704:Analysis of Variance; D002467:Cell Nucleus / Q000737:chemistry; D059248:Chemoradiotherapy; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000032:analysis*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D012189:Retrospective Studies; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases