720P - Pancreatic ductal adenocarcinoma: a homogeneous morphologically but molecularly heterogeneous tumor. Implications for its management
|Date||30 September 2012|
|Event||ESMO Congress 2012|
|Session||Poster presentation II|
|Topics|| Pancreatic Cancer
L. Faloppi1, A. Mandolesi2, M. Scartozzi1, C. Loretelli3, M. Bianconi1, A. Bittoni1, R. Giampieri1, M. Del Prete1, I. Bearzi2, S. Cascinu4
Pancreatic cancer has not achieved significant improvements in therapeutic results, probably due to a poor comprehension of the underlying molecular mechanisms. The aim of our study was to classify pancreatic tumors in categories from a molecular point of view, in order to better identify the main pathogenetic molecular alterations potentially useful as targets for new drugs. In 110 histological samples of pancreatic ductal adenocarcinoma were performed immunohistochemical evaluations of K-ras, stromal IL-6 (IL-6s), tumoral IL-6 (IL-6t), Cox-2, EGFR, Her2, Her3, MLH1, MSH2, MSH3 and molecular biology assessment of CD24, MUC6, HGF, MET, SMAD4, CDKN2A, PGF, VEGF-A/B, VEGFR-1/2, PDGFRB, WNT1, BMP4, stemness (ALCAM, PROM1, OCT3/4, CD44, LGR5,), Hedgehog (SHH, DHH, IHH, SMO, PTCH1, PTCH2), SPARC, NOTCH1, BRCA1, BRCA2. A preliminary analysis showed that the positivity of the inflammation mediators stromal IL-6, tumoral IL-6, Cox-2 allowed to differentiate two categories of pancreatic tumors: inflammatory tumors, associated with an intense desmoplastic reaction and alteration of EGFR and MLH1, and on the contrary tumors not associated with inflammation. Within these two groups statistical significant differences were found for EGFR and MLH1. An overexpression of EGFR was found in triple (97%) and double (88%) positive tumors, compared to negative or single positive (52%) (p0.0002). An higher rate of loss of MLH1 expression was found in triple positive tumors (69%), compared to double positive (40%) and negative or single positive (27%) (p0.02). Inflammation has been identified as a significant factor in the development of other malignancies. Mediators of the inflammatory pathway have been shown to be involved in proliferation, loss of tumor suppressor function, oncogene overexpression, all of which may lead to malignancy. Although definitive results concerning all the molecular factors analyzed will be presented during the ESMO 2012 congress, inflammation and its related molecular alterations may be specific targets for novel agents potentially useful for the treatment of these malignancies.Disclosure
All authors have declared no conflicts of interest.