Apoptotic proteins as prognostic markers and indicators of radiochemosensitivity in stage II/III rectal cancers

The expression of pro-apoptotic (Bax) and anti-apoptotic (mutated p53, Bcl-2, Bclxl) proteins was determined retrospectively using immunohistochemistry in pre-treatment biopsy samples from patients with rectal cancer treated with or without preoperative chemoradiation to investigate their role as prognostic markers and indicators of radiochemosensitivity.

Biopsy samples from 67 patients operated for stage II/III rectal cancer and enrolled in an active follow-up programme were examined 8-10 years after surgery. Thirty-three had been treated with immediate surgery followed, in selected cases, by adjuvant postoperative chemoradiation. Thirty-four had preoperative chemoradiation. Immunohistochemical staining was carried out using an automated immunostainer on sections of paraffin-embedded tissue.

Independent prognostic factors for rectal cancer death were pN status (hazard ratio 3.82; 95% CI 1.67-8.73) and a high level of Bclxl positivity (hazard ratio 4.75; 95% CI 2.10-10.72) according to multivariate regression analysis by stepwise selection. Bax expression was associated with downstaging and higher survival in irradiated patients (P = 0.0004).

Pretreatment evaluation of apoptotic Bax and anti-apoptotic Bclxl factors in biopsy samples of stage II/III rectal cancers may be helpful in selecting tumours that will respond to chemoradiation or in identifying patients who will have limited benefit from chemoradiation and should therefore be selected for a more aggressive systemic regimen.