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.