Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy.
OBJECTIVE
To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients.


METHODS
Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primary endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression.


RESULTS
Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive.


CONCLUSIONS
Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.
Unsal Kilic
Diclehan
D
Department of Radiation Oncology, Gazi University Faculty of Medicine, Ankara, Turkey. diclehan@yahoo.com
Uner
Aytug
A
Akyurek
Nalan
N
Erpolat
Petek
P
Dursun
Ayse
A
Pak
Yucel
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D012189:Retrospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis*
D000964:Antimetabolites, Antineoplastic; D009363:Neoplasm Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D002955:Leucovorin; D005472:Fluorouracil