236 - Polycystins 1 and 2 as novel prognostic markers in colorectal cancer

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Antonios N. Gargalionis
Authors A.N. Gargalionis1, G. Dalagiorgou1, P. Korkolopoulou2, C. Piperi1, G. Levidou2, C. Adamopoulos1, A. Zizi-Sermpetzoglou3, N. Tsavaris4, E.K. Basdra1, A.G. Papavassiliou1
  • 1Department Of Biological Chemistry, University of Athens, School of Medicine, 11527 - Athens/GR
  • 2First Department Of Pathology, Laikon General Hospital, University Of Athens, School of Medicine, Athens/GR
  • 3Department Of Pathology, Tzaneio General Hospital, Piraeus/GR
  • 4Oncology Unit, Department Of Pathophysiology, Laikon General Hospital, University of Athens, School of Medicine, Athens/GR

Abstract

Background/purpose

Polycystins 1 and 2 (PC-1 and PC-2) constitute a family of cellular proteins detected in a variety of epithelial cells throughout human tissues. They function as mechanosensors and contribute to cellular homeostasis through proliferation, differentiation and apoptotic processes. Nevertheless, their fundamental role in cell-to-cell mechanical interactions, cell–matrix communication, tissue morphogenesis and planar cell polarity connote their engagement in processes of oncogenesis, including invasion and metastasis. The aim of the study was to investigate the expression of PC-1 and PC-2 in colorectal cancer (CRC), identify possible correlations with histopathological characteristics and explore the underpinning signal transduction mechanisms.

Methods

The immunohistochemical expression of PC-1 and PC-2 was evaluated in paraffin sections of 144 CRC patients and the results were statistically correlated with clinical and pathologic parameters. Molecular mechanisms were explored by Western blot, immunofluorescence and flow cytometry in SW480 CRC cell line expressing PC-1 and PC-2.

Results

Significantly elevated cytoplasmic expression was observed for PC-1 and PC-2 in mucinous carcinomas (p = 0.0035 and p = 0.0001, respectively). High expression levels of PC-2 were correlated with advanced TNM stage (p = 0.0324) and depth of tumour invasion (p = 0.0311). High expression levels of PC-1 (p = 0.0078) and altered expression levels of PC-2 in the transition zone from normal to cancerous tissue (p = 0.0198) were associated with reduced five-year survival rate. Altered expression of PC-1 in the transition zone was correlated with higher chance of relapse for the patients (p = 0.0019). Experiments in SW480 cells revealed funneling of PC-1 and PC-2 function via mammalian target of rapamycin (mTOR) and p70S6 kinases.

Conclusions

Our findings suggest that PC-1 and PC-2 are implicated in the development of an aggressive phenotype in CRC, as well as in reduced five-year survival rate and cancer-free survival, thus constituting potential prognostic markers. Their function seems to be partially mediated by key molecules of the mTOR signaling pathway.

Disclosure

All authors have declared no conflicts of interest.