title: Chromosome instability in tumor resection margins of primary OSCC is a predictor of local recurrence.
abstract: The local recurrence rate in oral squamous cell cancer (OSCC) hardly decreases. This is partly due to the presence of (pre)malignant cells in the remaining tissue after resection, that may lead to the development of a new tumor in time. Detection of histologically (pre)malignant cells in the tumor resection margins should predict these patients at risk for recurrence, however this appears to be difficult in routine practice. Purpose of this study was to apply easy-to-use molecular tests for more accurate detection of (pre)malignant cells in histopathologically tumor-free margins, to improve diagnosis of patients at risk.
  
  
  
  42 patients with firstly diagnosed, radically resected primary OSCC with histopathologically confirmed tumor-free resection margins (treated between 1994 and 2003) were included. Inclusion criteria comprised of follow-up ⩾5years, and radical surgery without postoperative treatment. Formalin-fixed paraffine-embedded tissue sections of 42 tumors, 290 resection margins, and 11 recurrences were subjected to fluorescence in situ hybridization (FISH) to examine chromosome 1 and 7 copy number variations (CNV), and to p53 immunohistochemistry (IHC).
  
  
  
  11 out of the 42 patients developed a local recurrence within 5years. FISH analysis showed that nine of eleven recurrences exhibited CI in at least one of the resection margins (p=0.008). P53 overexpression and routine histopathologic classification were not correlated with recurrent disease. The presence of CI in the resection margins revealed a significantly worse progression-free survival (log-rank p=0.012).
  
  
  
  CI in the resection margins of OSCC can reliably identify patients at risk for developing a local recurrence.
authors.affiliation: Department of Oral and Craniomaxillofacial Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: damiana.pierssens@mumc.nl.
authors.forename: Damiana D C G
authors.initials: DDCG
authors.lastname: Pierssens
authors.affiliation: Department of Otorhinolaryngology, Head & Neck Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Borgemeester
authors.affiliation: Department of Otorhinolaryngology, Head & Neck Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Stijn J H
authors.initials: SJH
authors.lastname: van der Heijden
authors.affiliation: Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Carine J
authors.initials: CJ
authors.lastname: Peutz-Kootstra
authors.affiliation: Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Ruland
authors.affiliation: Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Annick M
authors.initials: AM
authors.lastname: Haesevoets
authors.affiliation: Department of Oral and Craniomaxillofacial Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Peter A W H
authors.initials: PAWH
authors.lastname: Kessler
authors.affiliation: Department of Otorhinolaryngology, Head & Neck Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kremer
authors.affiliation: Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Ernst-Jan M
authors.initials: EM
authors.lastname: Speel
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D043171:Chromosomal Instability; D002878:Chromosomes, Human, Pair 1; D002897:Chromosomes, Human, Pair 7; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009364:Neoplasm Recurrence, Local
keywords: Aneuploidy; Chromosomal instability; Copy number variation; FISH; Oral squamous cell carcinoma; Recurrence; Resection margins; p53