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The role of COX-2 and Ki-67 over-expression in the prediction of pathologic response of rectal cancer to neoadjuvant chemoradiation therapy.

BACKGROUND: The response to neoadjuvant chemoradiotherapy (CRT) is not the same among all cases with advanced rectal cancer.

AIMS: This study investigated the association between over-expression of the two molecular markers (Cyclooxygenase-2 [COX-2] and Ki-67) and tumor response to neoadjuvant therapy.

MATERIALS AND METHODS: In a retrospective cohort study, 55 patients with stage II-III rectal carcinoma were enrolled. All patients were treated with neoadjuvant therapy (45-50.4 Gy plus Capecitabine) between 2002 and 2009 in our institute. The pretreatment specimens were immunohistochemistry (IHC) stained for COX-2 and Ki-67 markers. The tumor response to neoadjuvant treatment was evaluated using a 5-point tumor regression grade (TRG) system. The induced inflammation and necrosis after CRT were also investigated. Statistical analysis was performed using SPSS version 11.5 and statistical significance was determined at P < 0.05.

RESULTS: The pathologic response to neoadjuvant treatment from complete response as (TRG = 1) through no response as (TRG = 5) was found in 10 (22.2%), 8 (17%), 6 (13.3%), 16 (35.6%), and 5 (11.1%) cases. In comparison with poor responders (TRG: 4, 5), patients with good response to neoadjuvant treatment (TRG: 1, 2) were associated with lower pretreatment mean COX-2 staining extent (72.9% vs. 22.8%, P < 0.001) as well as lower mean Ki-67 staining extent (70.7% vs. 28.5%, P < 0.001). High COX-2 staining and high Ki-67 index were significantly associated with more inflammation.

CONCLUSIONS: Over-expression of COX-2 and high Ki-67 index were associated with a poorer response to neoadjuvant CRT. These markers might be helpful to define those patients with rectal carcinoma who benefit more from neoadjuvant treatments.

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