P-039 - Increased expression of monocarboxylate transporters 1 and 4 and carbonic anhydrase IX in pancreatic ductal adenocarcinomas

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Pancreatic Cancer
Translational Research
Presenter A. Marques
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors A. Marques1, S. Granja2, A. Ferreira1, A. Silva1, S. Vilaça1, H. Marques1, F. Baltazar2
  • 1Hospital de Braga, Braga/PT
  • 2University of Minho, Braga/PT

Abstract

Introduction

Pancreatic ductal adenocarcinoma (PDA) has a particularly poor prognosis, even with the moderate improvements achieved by adjuvant treatments and new regimens of chemotherapy. Even in the presence of oxygen, cancer cells preferentially rely on glycolysis for energy production, leading to an increase production of lactate. Monocarboxylate transporters (MCTs), proteins involved in the transport of lactate across the plasma membrane, as well as carbonic anhydrase IX (CAIX), an established marker of hypoxia, appear to play an important role in solid tumours. Since data concerning MCTs and CAIX expression in PDA are scarce, the present study aimed to assess the expression of MCT1, MCT4 and CAIX in a series of PDA and evaluate its clinicopathological significance.

Methods

We analyzed and compared the immunohistochemical expression of MCT1, MCT4 and CAIX in a series of 51 PDA samples and in 16 adjacent normal epithelium samples. The association between expression patterns and clinicopathological data was assessed.

Results

PDA samples were obtained from 51 patients, 26 males, with median age at diagnosis of 63 years (30-82) and median overall survival of 8.6 months (0.2-74.5). Patients were diagnosed with stage III or IV disease in 71% of the cases. Levels of CA19.9 were elevated in 74.5% of the patients. Most tumors were located in the pancreatic head (70%) with a median size of 38 millimeters (10-95). Vascular invasion was observed in 69% of the samples retrieved from surgical excision specimens, which showed mainly good or moderate degree of differentiation (75%). An increased expression of MCT1 (p = 0.006), MCT4 (p < 0.001) and CAIX (p < 0.001) was observed in PDA when compared to adjacent normal tissue. MCT1 and MCT4 expression was not correlated with CAIX expression. None of the clinicopathological parameters previously described was significantly associated with the expression increase, namely overall survival (OS).

Conclusion

This study shows an increased expression of the MCT1, MCT4 and CAIX in PDA, indicating a possible contribution of cancer cell metabolic adaptations in PDA development and progression. However, these findings had no relevant clinicopathological association, including no impact on OS. The small sample size might be a limitation; therefore larger studies are needed to clarify any clinical relation of these findings. The increased expression of CAIX and especially MCT1 and MCT4, might justify their exploitation as therapeutic targets.