Molecular responses of rectal cancer to preoperative chemoradiation.
OBJECTIVE
Some rectal cancers respond well to preoperative neoadjuvant therapy while others are inherently resistant or develop resistance during the treatment. To understand the mechanism underlying these differences, several markers that might be prognostic or predictive of downstaging in response to chemoradiotherapy in patients with rectal cancer were evaluated.


METHODS
Thirty patients were enrolled in this study. All were treated with preoperative chemoradiation (45Gy in 25 fractions+5-FU). Paraffin-embedded sections obtained before and after therapy were stained by H&E, for COX-2, and Ki67. In addition, osteopontin and IL-6 concentrations were determined in blood samples obtained before, during, and after therapy.


RESULTS
COX-2 expression increased in 67% (n=8/12) of the patients from a median of 0% before to 74% after therapy (p=0.009). Ki67 median positivity diminished from 90% to 45% in 83% (n=10/12) of cases (p=0.007). Osteopontin expression showed no significant changes during therapy, whereas IL-6 expression levels increased in 70% (n=19/27) of all patients (p<0.001). For osteopontin and IL-6, patients with a complete response tended to have lower pre-therapy levels. Moreover, osteopontin was much higher before (p=0.02) and after therapy (p=0.01) in patients who later developed metastases.


CONCLUSIONS
Chemoradiotherapy seems to affect expression of COX-2 and Ki67 which indicates that these proteins might be of importance in predicting long-term outcome. Moreover, osteopontin might be a marker of metastases.
Debucquoy
Annelies
A
Department of Radiation Oncology and Experimental Radiation, Leuven Cancer Institute, University Hospital Leuven, Belgium. annelies.debucquoy@med.kuleuven.be <annelies.debucquoy@med.kuleuven.be>
Goethals
Laurence
L
Geboes
Karel
K
Roels
Sarah
S
Mc Bride
William H
WH
Haustermans
Karin
K
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D053495:Osteopontin / Q000097:blood / Q000378:metabolism; D011300:Preoperative Care / Q000379:methods; D011379:Prognosis; D011720:Pyrazoles / Q000627:therapeutic use; D012004:Rectal Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D013449:Sulfonamides / Q000627:therapeutic use
D014408:Biomarkers, Tumor; D015850:Interleukin-6; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D053495:Osteopontin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib; D005472:Fluorouracil