660P - Expression of caspase-3 predicts prognosis in advanced noncardia gastric cancer

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Gastric Cancer
Translational Research
Presenter Sousana Amptoulach
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors S. Amptoulach, A. Lazaris, M. Karadima, D. Boulamatsis, N. Kavatzas, E. Patsouris, N. Tsavaris
  • Oncology Unit, Laikon General Hospital, Athens University School of Medicine, 11527 - Athens/GR

Abstract

Aim

Caspases are proteolytic enzymes that play an essential role in apoptosis, which may affect tumor growth. We aimed to investigate the potential relation of the expression of caspase-1, -2 and -3 with response to therapy and overall survival in patients with advanced noncardia gatric cancer.

Methods

Tumor tissue samples from consecutive patiients with noncardia gastric cancer stage IV- treated in our institution- between 01/1991- 04/2011 were retrospectively analyzed for the expression of caspase-1, -2 and -3. Apoptosis was expressed as the DNA apoptotic index,(terminal deoxynucleotidyl transfrase-mediate deoxyuridin triphosphate-biotin nick end labeling method). Patient files were scrutinized and relevant data, such as the Karnofsky performance status and location of metastases, were registered. All patients were followed-up until death.

Results

359 patients were included (mean age 60.2 yr; 35% female; 53% underwent palliative surgery; mean survival time 38 wks). Caspase-1 was expressed in 57%, caspase-2 in 74% and caspase-3 in 44% of tumors. All patients but 8 received palliative chemotherapy and 24% of patients had a complete/partial response to chemotherapy while 32% had stable and 44% progressive disease. Caspase-3 expression was related to a higher DNA apoptotic index (p < 0.05). Expression of caspase-3 was more common in patients with progressive disease (54%) compared to stable disease (42%) and response to chemotherapy (27%; p < 0.05).Overall survival was lower among those with vs those without caspase-3 expression (log-rang test p < 0.05). After adjustment for confounders wihth logistic regression analysis, tumor expression of caspase-3 was an independent predictor of poor response to treatment (OR 0.36, 95% CI 0.17-0.78). Similarly, in Cox multivariate regression analysis, the expression of caspase-3 was an independent predictor of poor survival (HR 1.50, 95% CI 1.20-1.87). Expression of caspase-1 and -2 were found to have no impact on response to treatment or survival (p > 0.05).

Conclusions

Expression of caspase-3, but not caspase-1 or -2, is a predictor of poor response to treatment and survival in advanced gastric cancer. Further studies are needed to fully elucidate the prognostic value of caspase in gastric cancer.

Disclosure

All authors have declared no conflicts of interest.