618 - An exploratory analysis of AMPK and ACC activation in colorectal primary tumors and their corresponding metastasis

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Francesca Bergamo
Authors F. Bergamo1, G. Griguolo2, E. Zulato3, G. Esposito3, M. Nardin3, C. Mescoli4, M. Rugge5, V. Zagonel6, S. Lonardi7, S. Indraccolo3
  • 1U.o.oncologia Medica, Istituto Oncologico Veneto -IRCSS, 35128 - Padua/IT
  • 2University Of Padova - School Of Medicine, University of Padova - School of medicine, Padova/IT
  • 3Istituto Oncologico Veneto - Irccs, Istituto Oncologico Veneto - IRCCS, Padova/IT
  • 4Istituto Di Anatomia Patologica, University of Padova, Padova/IT
  • 5Pathology And Cytopathology Unit, University of Padova, 35137 - Padova/IT
  • 6Department Of Oncology, Istituto Oncologico Veneto, 35128 - Padua/IT
  • 7Medical Oncology Unit 1, Istituto Oncologico Veneto -IRCSS, 35128 - Padua/IT

Abstract

Background

AMPK is a well known oncosuppresor, with prognostic significance in many neoplasms; it acts as a central metabolic sensor in cells, activated in energy-stress conditions. ACC is a central enzyme in cell metabolism activated through phosphorilation by AMPK. In pre-clinical models AMPK activation level correlates with necrotic response when tumors are treated with Bevacizumab. Our goal was 1) to evaluate the concordance of these markers' activation in primary tumours and in the corresponding metastasis, 2) to investigate their correlation with clinical data, in particular radiological response to FOLFIRI plus Bevacizumab.

Methods

This retrospective study analyzed histological pre-treatment material from 32 patients with mCRC treated with FOLFIRI-Bevacizumab to evaluate AMPK and ACC activation in primary CRC and its metastasis using immunohistochemistry. The intensity was scored from 0 (negative) to 3 (intense), and then dichotomized in low (0-1) and high (2-3) activation categories. pAMPK and pACC intensity scores in primary tumors and metastasis were compared using Spearman's correlation test. Radiological response has been going to be evaluated using both RECIST and morphologic criteria (Chun Criteria).

Results

pAMPK was defined high in 20 (63%) primary and in 21 (66%) of the corresponding metastases while pACC in 23 (72%) primary tumors and 19 (59%) metastases. As attended from biological knowledge, AMPK and ACC activation correlated significatively in primary tumors (p = 0.0007). ACC activation in primary tumors correlated significatively with its activation in their metastasis (p = 0.04), while AMPK activation in primary tumors and in metastasis showed a correlation not reaching statistical significance (p = 0.13). Correlation between AMPK and ACC activation and radiological morphological response was still not possible at time of writing.

Conclusions

AMPK and ACC activation showed a weak correlation in primary and metastastatic tumors, possibly due to the small number of patients and the higher heterogeneity of the metastatic tissue. The opportunity to use these biomarkers to predict a necrotic response to bevacizumab treatment is under investigation.

Disclosure

All authors have declared no conflicts of interest.