Absence of cyclooxygenase-2 protein expression is a predictor of tumor regression in rectal cancer treated with preoperative short-term chemoradiotherapy.
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.
Kobayashi
Hirotoshi
H
Department of Surgery, National Defense Medical College, Saitama, Japan. h-kobayashi.srg2@tmd.ac.jp
Hashiguchi
Yojiro
Y
Ueno
Hideki
H
Shinto
Eiji
E
Kajiwara
Yoshiki
Y
Mochizuki
Hidetaka
H
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
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D051546:Cyclooxygenase 2