Clinicopathological features and response to platinum-based chemotherapy (PBC) in pancreatic neuroendocrine carcinoma (pNEC): Updated results of Japan pNEC study.

Abstract

e15652 Background: The WHO classified pancreatic neuroendocrine Neoplasms (pNEN) in 2010 as G1, G2, and NEC. However, pNEC is suspected to include heterogeneous disease entities, but is still not fully studied. We aimed to clarify the clinicopathological/molecular characteristics of pNECs. Methods: A total of 100 cases clinical data and pathological slides originally diagnosed as pNEC by the WHO in 2010(WHO-NEC) were retrospectively collected from 31 institutes. Expert pathologists were reassessed all cases slide using the designed protocol and reclassified as well differentiated NET (NET-G3), small cell NEC (SCNEC), and large cell NEC (LCNEC) by morphological features. Results: Thirty cases were eliminated mostly because acinar cell carcinoma, NET-G2 and malignant tumor not otherwise specified, and were eliminated. Remained 70 cases were subclassified into NET-G3 (n = 21, 30%), SCNEC (n = 31, 44.3%), and LCNEC (n = 18, 25.7%). Comparisons of NET-G3 vs. SCNEC vs. LCNEC revealed the following traits: ENETS stage IV (%): 76, 81, 78; median Ki67 LI (%): 28.5 (15–53), 85 (50–100), 70.0 (22–90); abnormal Rb expression (%): 0, 59, 47; KRAS mutations (%): 0, 48, 50; response rate (RR) to PBC (%): 0, 60, 44.4; and overall survival (days): 1255, 196, 340, respectively. When KRAS divided mutation (n = 20) and wild type group (n = 42), RR to PBC as 1st line treatment was 77% vs. 23%. In the same manner, when Rb immune stain divided negative (n = 24) and positive (n = 41), RR to PBC as 1st line treatment was 80% vs. 23.8%. In terms of double abnormalities of Rb expression and KRAS mutation, positive and negative predictive values of response to PBC as 1st line treatment were 100% (7/7, 97.5%CI; 59.0–100) and 69.2% (26/18, 95%CI; 48.2–85.7), respectively. Conclusions: In this retrospective study, WHO-NEC include 30% NET-G3. NET-G3 is clinically and genetically different from SCNEC and LCNEC. As for chemotherapy, Mutated KRAS and/or Rb immunonegativity in tumors with pNEC is associated with response to PBC. Double abnormalities of KRAS mutation and Rb expression may be a strong predictor of PBC.