title: Absence of cyclooxygenase-2 protein expression is a predictor of tumor regression in rectal cancer treated with preoperative short-term chemoradiotherapy.
abstract: OBJECTIVE
  Neoadjuvant chemoradiotherapy followed by total mesorectal excision has become the standard of care for patients with locally advanced rectal cancer. This study was designed to determine whether pretreatment cyclooxygenase-2 and p53 protein expression were predictors of histopathologic response in patients with rectal cancer treated with preoperative short-term chemoradiotherapy.
  
  
  METHODS
  Fifty-two patients with low rectal cancer received short-term preoperative chemoradiotherapy (20 Gy given in 5 daily doses of 4 Gy and concurrent administration of Tegafur/Uracil 400 mg/day), followed by total mesorectal excision. Cyclooxygenase-2 and p53 protein expression were measured by immunohistochemistry before and at the time of resection. Tumor regression grading was evaluated according to the criteria by Rodel (Grade 4, complete regression; Grade 3, regression >50 percent; Grade 2, 25-50 percent; Grade 1,<25 percent; and Grade 0, no regression).
  
  
  RESULTS
  Two patients had a pathologic complete response. Good response (Grade 3 + 4) was found in 57.7 percent of the resected specimens. Cyclooxygenase-2 was expressed in 80.8 percent of patients before chemoradiotherapy and in 100 percent after chemoradiotherapy. The rates of good response (Grade 3 + 4) were significantly associated with lack of cyclooxygenase-2 expression before chemoradiotherapy (P = 0.021). However, there was no correlation between p53 protein expression and tumor regression grading.
  
  
  CONCLUSIONS
  Patients with tumor lacking cyclooxygenase-2 expression before chemoradiotherapy are more likely to demonstrate good response to treatment. Cyclooxygenase-2 protein expression may be a marker for response to chemoradiotherapy in patients with rectal cancer.
authors.affiliation: Department of Surgery, National Defense Medical College, Saitama, Japan. h-kobayashi.srg2@tmd.ac.jp
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Hashiguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kajiwara
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Mochizuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D003082:Colectomy; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D051546:Cyclooxygenase 2