Low Mmp 9 and VEGF levels predict good oncologic outcome in mid and low rectal cancer patients with neoadjuvant chemoradiation.

Background: The aim of this study was to evaluate apoptotic (Bcl-2, Bax expression, caspase-3 activity, and cytochrome-c) and angiogenic (MMP-9 levels and VEGF expression) markers in operable rectal cancer patients who were treated with preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Understanding these factors will facilitate the identification of potential pathological responders before treatment, leading to better local control and survival rates.

Methods: Between March 2006 and March 2008, 29 patients withTNM Stage III (cT3 N+) mid or low rectal cancer were included in this study. Our sample consisted of 17 males (58.6%) and 12 females (41.4%). The median age was 60 years (range 24-88 years). Biopsy samples were taken from different portions of the tumors using flexible endoscopy before neoadjuvant CRT. Preoperatively, all patients received radiation (45-50.4 gray (Gy) in 25 cycles with concurrent 5-florouracil (5-FU) chemotherapy.

Results: A complete response was observed in 7 of 29 patients (24%). Bax staining was negative in 1 of the 7 patients (14%) in the pathological complete response (PCR) group and in 18 of the 22 patients (82%) in the no pathological complete response (noPCR) group (p = 0.001). MMP-9 and VEGF levels were higher in the noPCR group than the PCR group (p = 0.04, p = 0.05 respectively). No statistically significant differences were found between VEGF and MMP-9 levels in nodal downstaging. No statistically significant relationships were found between the other apoptotic factors (Bcl 2, cytochrome-c, and caspase-3 activity) and pathological response rate (p > 0.05).

Conclusion: In neoadjuvant CRT patients, high levels of Bax expression and low levels of VEGF and MMP-9 expression on preoperative biopsies indicate that the patient will potentially be a good pathological responder.