698P - COX-2 status modulates the activation of Hedgehog pathway and consequently the expression of stem cell markers in patients with pancreatic ductal a...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Pancreatic Cancer
Translational Research
Presenter Alessandro Conti
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors A. Conti1, M. Santoni2, A. Bittoni3, K. Andrikou4, A. Lanese5, C. Pellei6, C. Loretelli3, A. Mandolesi7, S. Alfonsi7, M. Scarpelli7, S. Cascinu6
  • 1Clinica Di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche, 60126 - Ancona/IT
  • 2Clinica Di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche, Ancona/IT
  • 3Clinica Di Oncologia Medica, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, Ancona/IT
  • 4Medical Oncology, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, 60126 - Ancona/IT
  • 5Clinica Di Oncologia Medica, Ospedali Riuniti di Ancona, 60019 - Ancona/IT
  • 6Clinica Di Oncologia Medica, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, 60126 - Ancona/IT
  • 7Anatomia Patologica, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche,, Ancona/IT

Abstract

Aim

Inflammation is a key driver in the development of pancreatic ductal adenocarcinoma (PDAC). Cyclooxygenase-2 (COX-2) and Interleukin (IL)-6 are key modulators of inflammation and act as a potential link between chronic pancreatitis and subsequent carcinogenesis. In this study, we analyzed the association between COX-2 and IL-6 status and the expression of Hedgehog signaling pathway and stem cell markers and their relationship with the clinico-pathological features and prognosis of PDAC patients.

Methods

The expressions of COX-2 and IL-6 were examined using immunohistochemistry in 79 resection specimens of PDAC. The expression of the Hedgehog components SHH, IHH, DHH, SMO, PTCH1, PTCH2, and stem cell markers CD24, CD44, OCT3/4 and PROM1 were analyzed by qRT-PCR. The correlation among gene expression levels was performed by the Pearson product moment correlation method. Survival analysis was conducted via Kaplan-Meier product-limit method.

Results

49 patients (62%) had COX-2+ tumors, while 37 patients (47%) had IL-6+ tumors. SHH (p = 0.001), IHH (p = 0.011) and SMO (p = 0.040) were significantly more expressed in patients COX-2+. In addition, IHH was significantly more expressed in patients with IL-6+ tumors (p = 0.040). CD44 expression was associated with DHH (rho = 0.742), IHH (rho = 0.826) and SMO (rho = 0.899). PROM1 expression was associated with DHH (rho = 0.772), IHH (rho = 0.847) and SMO (rho = 0.915). T stage was higher in patients with COX-2+ (p = 0.020), whereas no associations were found between COX-2 and node involvement (p = 0.071) or grading (p = 0.273) as well as between IL-6 expression and the clinico-pathological characteristics of these patients. No significant differences in terms of survival were found based on COX-2 or IL-6 status.

Conclusions

Taken together, our data suggest for a model in which COX-2 expression modulates the activation of the Hedgehog pathway and, subsequently, the expression of stemness markers. These data may lead to a better characterization of patients to include in clinical trials in order to develop future therapeutic strategies.

Disclosure

All authors have declared no conflicts of interest.