1140PD - Finding molecular subgroups of worse prognosis studying the microenvironment of gastro-entero-pancreatic neuroendocrine tumours (GEP-NET).

Date 29 September 2014
Event ESMO 2014
Session Neuroendocrine & endocrine tumours and CUP
Topics Neuroendocrine Cancers
Pathology/Molecular Biology
Presenter Jorge Barriuso
Citation Annals of Oncology (2014) 25 (suppl_4): iv394-iv405. 10.1093/annonc/mdu345
Authors J. Barriuso1, E. Bernal1, L.G. Pastrian2, J. Martinez1, E. Diaz1, V. Heredia1, M. Miguel1, C. Alvarez-Escola3, J. Castell4, J. Feliu1, E. Burgos2, M. Mendiola1
  • 1Translational Oncology And Pathology Group, La Paz University Hospital, 28046 - Madrid/ES
  • 2Department Of Pathology, La Paz University Hospital, 28046 - Madrid/ES
  • 3Department Of Endocrinology, La Paz University Hospital, 28046 - Madrid/ES
  • 4Department Of Gastrointestinal Surgery, La Paz University Hospital, 28046 - Madrid/ES

 

Abstract

Aim

Tumour suppressor genes, CDKN1B and PTEN, are commonly altered in GEP-NET. However, their role is not completely understood yet. The aim of this study was to link the expression of their products (p27 and PTEN) with proteins of the GEP-NET microenvironment.

Methods

Formalin-fixed and paraffin-embedded samples (FFPEs) of patients (pts) who underwent surgery for GEP-NET and their clinical data were collected consecutively from 1980 to 2012. The study was approved by the local Ethics Committee. Tissue microarrays were constructed from non-necrotic areas of tumour foci. We performed a stratified analysis of proteins related to the extracellular matrix and the epithelial to mesenchymal transition process by inmunohistochemistry-measured PTEN and P27. Kaplan-Meier method and log rank test was used for the univariate survival analysis and Cox regression was used for the multivariate analysis (MSA).

Results

A total of 115 FFPEs were analysed. Median follow up was 12 years. Median age was 46 years; 49.6% female; 67.8% intestinal. PTEN was evaluated as presence vs absence and P27 as strong nuclear staining vs weak or absence. P27 and PTEN were independent prognostic factors for disease free survival (DFS) when adjusted by grade and stage, p = 0.028 and p = 0.023 respectively. Within the PTEN negative subgroup, LOXL2 + conferred protection for relapse, p < 0.001 and remained significant in the MSA, HR: 0.06 95%CI: 0.01-0.63; B-catenin nuclear expression (BCATn) was a marker of bad prognosis, p = 0.043. Within P27- cases, LOXL2 + had longer DFS (p = 0.01) and a HR: 0.25 95%CI: 0.08-0.83 in the MSA; CXCR4 + and BCATn had shorter DFS (p = 0.035 and p = 0.005) but were not significant in the MSA.

CXCR4 + CXCR4- LOXL2 + LOXL2- BCATm BCATn
P27- 55.9 (0.1-132.8) NR NR 7.2 (4.6-7.8) NR 124.1 (16.7-231.5)
PTEN- NC NC NR 0.4 (0.1-2.2) NR 124.1 (35.3-212.9)

DFS medians calculated in months by Kaplan Meier method. BCATm: ß-catenin membranous staining. NR: not reached. NC: not calculated.

Conclusions

Patients with P27– LOXL2– or PTEN– LOXL2– had the worst prognosis. These findings warrant further in vitro mechanistically experiments and prospective clinical analysis.

Disclosure

All authors have declared no conflicts of interest.