Session: Endocrine/Head & Neck and HPB Virtual Poster Grand Rounds
V35: All Roads Lead to Rome: Terminal Phenogenotypes of Pancreatic Ductal Adenocarcinoma Do Not Differ Regardless of the Evolutionary Precursor. a Case-control Study
GI instructor in minimally invasive GI surgery Moffitt Cancer Center Tampa, Florida, United States
Disclosure: Disclosure information not submitted.
Participants should be aware of the following financial/non-financial relationships:
Samer A. Naffouje, M.D.: Disclosure information not submitted.
Introduction: PanIN and IPMN are known precursors of pancreatic ductal adenocarcinoma (PDAC). However, little is known about the prevalence, molecular profiles, and associated survival outcomes of these PDAC precursors (PP)
Methods: We included patients with resected pancreatic malignancies without neoadjuvant therapy. Study group included patients with PDAC vs. control group with non-PDAC. Patients who had PanIN as PP were propensity-matched to those with IPMN to compare local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and overall survival (OS). Patients with available RNA- and DNA-sequencing were analyzed to compare molecular subtypes, expression of a 15-gene prognostic signature, and mutations in a 5-gene panel (KRAS/TP53/GNAS/SMAD4/RNF43)
Results: 505 patients were included, 370 had PDAC vs. 135 had non-PDAC. In PDAC group, 329 patients (88.9%) had a PP (219 patients (59.2%) had PanIN vs.110 (29.7%) had IPMN), whereas non-PDAC group had only 46 patients (34%) with PP (p< 0.001). In PDAC patients we propensity-matched 97 patients with PanIN to 97 patients with IPMN. Median follow up was 21 months. No difference was detected in LRFS (21.0±2.5 vs. 25.0±3.9 mos), DRFS (13.0±2.3 vs. 15.0±1.8 mos), or OS (22.0±3.3 vs. 28.0±2.9 mos) (p=NS for all). 73 patients had RNA-sequencing and no difference was detected in PDAC molecular subtyping or in the expression of the prognostic 15-gene signature. DNA-sequencing was available for 16 patients, (12 PanIN & 4 IPMN). Analysis of the 5-gene panel identified KRAS mutation as the most common (13/16), followed by TP53 (11/16). GNAS mutation was detected in 6 patients divided equally between PanIN and IPMN (3 vs. 3)
Conclusions: PPs are more common than reported (88.9%) and statistically more prevalent in PDAC vs. non-PDAC (34%). PDACs arising from PanIN had comparable survival to those arising from IPMN, supported by resemblance in molecular subtyping, prognostic multigene signature, and DNA mutational analysis. Our study suggests that despite following different evolutionary pathways, PPs produce PDACs with similar phenogenotypes once they convert into an invasive malignancy
Learning Objectives:
Upon completion, participants will be able to understand the prevalence of PDAC precursors in resected PDAC specimens, as well as the distribution of PanIN vs. IPMN in these specimens
Upon completion, participants will be able to learn that PDACs arising from different precursors share similar molecular subtypes and DNA mutational profile
Upon completion, participants will be able to learn that PDACs arising from PanIN have comparable survival outcomes compared to those arising from IPMN in a matched analysis
