title: Impact of neoadjuvant therapy on cancer-associated fibroblasts in rectal cancer.
abstract: OBJECTIVE
  Cancer-associated fibroblasts (CAFs) are increasingly recognised as promoters of tumour progression. It is poorly investigated whether cancer management protocols, such as neoadjuvant radio(chemo)therapy, have an impact on CAFs and, by consequence, on tumour progression. This prompted us to study the impact of neoadjuvant radio(chemo)therapy on the α-SMA/epithelial area ratio in rectal cancer, and the impact of this ratio on recurrence-free survival.
  
  
  METHODS
  Immunohistochemistry for the CAF marker α-SMA and the proliferation marker Ki67 was performed on sections from 98 rectal cancers of which 62 had undergone neoadjuvant radio(chemo)therapy.
  
  
  RESULTS
  Computer-assisted quantitative analysis showed that the α-SMA/neoplastic epithelial area ratio was higher after neoadjuvant therapy, and that rectal cancers with high α-SMA/epithelial area ratio had low proliferation rates. Interestingly, the α-SMA/epithelial area ratio was an adverse prognostic factor with regard to recurrence-free survival in univariate analysis. In addition, multivariate analysis showed that an α-SMA/epithelial area ratio above 1 provides an independent prognostic value associated with a poor recurrence-free survival.
  
  
  CONCLUSIONS
  These results suggest that neoadjuvant treatment has an impact on CAFs in rectal cancer. The correlation of CAFs with decreased recurrence-free survival and abundant experimental data in the literature suggest that under certain circumstances, not yet very well understood, CAFs may favour tumour progression.
authors.affiliation: Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Laurine
authors.initials: L
authors.lastname: Verset
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Universiteit Gent (UG), Ghent, Belgium.
authors.forename: Joke
authors.initials: J
authors.lastname: Tommelein
authors.affiliation: DIAPATH-CMMI Center for Microscopy and Molecular Imaging, Gosselies, Belgium; Laboratories of Image, Signal Processing and Acoustics (LISA), ULB, Brussels, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Moles Lopez
authors.affiliation: DIAPATH-CMMI Center for Microscopy and Molecular Imaging, Gosselies, Belgium; Laboratories of Image, Signal Processing and Acoustics (LISA), ULB, Brussels, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Decaestecker
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Universiteit Gent (UG), Ghent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Boterberg
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Universiteit Gent (UG), Ghent, Belgium.
authors.forename: Elly
authors.initials: E
authors.lastname: De Vlieghere
authors.affiliation: Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium; DIAPATH-CMMI Center for Microscopy and Molecular Imaging, Gosselies, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Salmon
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Universiteit Gent (UG), Ghent, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Mareel
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Universiteit Gent (UG), Ghent, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Bracke
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Universiteit Gent (UG), Ghent, Belgium. Electronic address: olivier.dewever@ugent.be.
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
authors.affiliation: Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: pieter.demetter@erasme.ulb.ac.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Demetter
mesh_terms: D000199:Actins / Q000378:metabolism / Q000528:radiation effects; D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000473:pathology / Q000528:radiation effects*; D020360:Neoadjuvant Therapy / Q000379:methods; D011379:Prognosis; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: Cancer-associated fibroblast; Myofibroblast; Neoadjuvant therapy; Rectal cancer