title: Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiotherapy for rectal cancer?
abstract: BACKGROUND
  Numerous molecular markers have been investigated as potential predictors of tumor responses to preoperative chemoradiotherapy (preCRT) for rectal cancer.
  
  
  OBJECTIVE
  To develop a system in which biomarkers are used to predict the likelihood of a pathologic complete response (pCR) to preCRT.
  
  
  METHODS
  This is a retrospective analysis of tumor specimens collected prior to preCRT from 81 patients who underwent curative resection for primary rectal adenocarcinoma between June 2008 and February 2012.
  
  
  METHODS
  Using tissue microarrays and immunohistochemistry, expression levels of twelve candidate biomarkers (p53, p21, Bcl2, Bax, EGFR, Cox-2, MLH-1, MSH-2, Ku70, VEGF, TS, Ki-67) were evaluated in paraffin-embedded tumor samples collected before preCRT. The correlation between biomarker expression levels and the pathologic response to preCRT was assessed based on histopathological staging (pTNM) and tumor regression grade (TRG).
  
  
  RESULTS
  Expression levels of 4 biomarkers (p53, VEGF, p21, Ki67) correlated with pCR. Patients showing low expression of p53 and/or high expression of VEGF, p21, and Ki67 exhibited a significantly greater pCR rate. A scoring system devised so that one point was given for each biomarker whose expression level correlated with pCR (score range: 0-4) showed that 1 of 26 patients with scores of 0 to 1 achieved pCR, whereas 26 of 55 patients with scores of 2 to 4 achieved pCR (3.8% vs. 47.3%, p < 0.001). For prediction of pCR, the scoring system showed 96.3% sensitivity, 46.3% specificity, a 47.3% positive predictive value, and a 96.2% negative predictive value.
  
  
  CONCLUSIONS
  Immunohistochemistry has limitations related to reproducibility and the ability to provide quantitative information. In addition, this study lacks test and validation sets.
  
  
  CONCLUSIONS
  Expression levels of 4 biomarkers correlated with pCR after preCRT for rectal cancer. A scoring system based on levels of biomarker expression showed good sensitivity and negative predictive value for pCR.
authors.affiliation: 1Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea 2Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea 3Department of Medical Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea 4Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Hur
authors.forename: Nam Kyu
authors.initials: NK
authors.lastname: Kim
authors.forename: Byung Soh
authors.initials: BS
authors.lastname: Min
authors.forename: Seung Hyuk
authors.initials: SH
authors.lastname: Baik
authors.forename: Kang Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Woong Sub
authors.initials: WS
authors.lastname: Koom
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D012189:Retrospective Studies; D012812:Sigmoidoscopy; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D002955:Leucovorin; D005472:Fluorouracil