title: Predictive markers of response to neoadjuvant therapy in rectal cancer.
abstract: BACKGROUND
  Neoadjuvant therapy followed by radical surgery is the standard treatment in locally advanced rectal cancer. It is important to predict the response because the treatment has side effects and is costly. The aim of this study was to establish the relationship among clinical, pathologic, and molecular biomarkers and the response to neoadjuvant therapy.
  
  
  METHODS
  A total of 130 patients with locally advanced mid and low rectal cancer who underwent long-course radiotherapy with 5-FU based chemotherapy followed by radical surgical resection were included in the study. Clinical and pathologic data were collected. Paraffin-embedded sections obtained in diagnostic biopsies were assessed by immunohistochemical staining for molecular markers and classified using a semiquantitative method. Results were related with T-downstaging and tumor regression grade using Mandard scoring system on surgical specimens.
  
  
  RESULTS
  Pathologic complete response was found in 19 patients (14.6%), while in another 18 (13.8%) only minor residual disease was seen in the rectal wall. T-downstaging was observed in 63 (48.5%). The average of lymph node retrieval in the surgical specimens was 9.4. Regarding predictive markers of response, there was significant correlation between the expression of B-cell lymphoma 2 (P = 0.005), β-catenin (P = 0.03), vascular endothelial growth factor (P = 0.048) and apoptotic protease activating factor 1 (P = 0.03), tumor differentiation grade (P < 0.001), and response in the univariate analysis. T-downstaging was associated with vascular endothelial growth factor expression (P = 0.03) and tumor differentiation grade (P < 0.001). Significant parameters found in the multivariate analysis were tumor differentiation grade and Bcl-2 expression.
  
  
  CONCLUSIONS
  Pathologic and molecular biomarkers in the diagnostic biopsies may help us predict tumor response to chemoradiation in rectal cancer patients.
authors.affiliation: Department of General Surgery, Hospital San Agustín, Avilés, Spain. Electronic address: luisjgf@gmail.com.
authors.forename: Luis Joaquín
authors.initials: LJ
authors.lastname: García-Flórez
authors.affiliation: Colorectal Section, Department of General Surgery, University Central Hospital of Asturias, Oviedo, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gómez-Álvarez
authors.affiliation: Colorectal Section, Department of General Surgery, University Central Hospital of Asturias, Oviedo, Spain.
authors.forename: Ana Madalina
authors.initials: AM
authors.lastname: Frunza
authors.affiliation: Department of Surgery, Biotechnological and Biomedical Assays Unit, University of Oviedo, Oviedo, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Barneo-Serra
authors.affiliation: Department of Pathology, University Central Hospital of Asturias, Oviedo, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez-Alonso
authors.affiliation: Department of Pathology, University Central Hospital of Asturias, Oviedo, Spain.
authors.forename: Manuel Florentino
authors.initials: MF
authors.lastname: Fresno-Forcelledo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Chemoradiotherapy; Neoadjuvant therapy; Predictive biomarkers; Rectal cancer